Aims. To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope. Methods. Based on sample size calculation, 70 male C57BL/6 mice were randomly assigned to three surgery groups: DMM aided by a stereomicroscope; DMM by naked eye; or sham surgery. The group information was blinded to researchers. Mice underwent static weightbearing, von Frey test, and gait analysis at two-week intervals from eight to 16 weeks after surgery. Histological grade of OA was determined with the Osteoarthritis Research Society International (OARSI) scoring system. Results. Surgical DMM with or without stereomicroscope led to decrease in the mean of weightbearing percentages (-20.64% vs -21.44%, p = 0.792) and paw withdrawal response thresholds (-21.35% vs -24.65%, p = 0.327) of the hind limbs. However, the coefficient of variation (CV) of weight-bearing percentages and paw withdrawal response thresholds in naked-eye group were significantly greater than that in the microscope group (19.82% vs 6.94%, p < 0.001; 21.85% vs 9.86%, p < 0.001). The gait analysis showed a similar pattern. Cartilage degeneration was observed in both DMM-surgery groups, evidenced by increased OARSI scores (summed score: 11.23 vs 11.43, p = 0.842), but the microscope group showed less variation in OARSI score than the naked-eye group (CV: 21.03% vs 32.44%; p = 0.032). Conclusion. Although surgical DMM aided by stereomicroscope is technically difficult, it produces a relatively more homogeneous OA model in terms of the discrete degree of pain behaviours and histopathological grading when compared with surgical DMM without stereomicroscope. Cite this article: Bone Joint Res 2022;11(8):518–527

We present the first reported case of symptomatic medial dislocation of the medial meniscus in a patient who had no previous history of trauma and who had an otherwise normal knee. The treatment of instability of the medial meniscus is controversial and studies have indicated that certain individuals without a firm meniscal bony insertion may be predisposed to meniscal dislocation. In our patient, the meniscal instability interfered with daily activities. Operative stabilisation by reconstruction of the meniscotibial ligaments cured the symptoms

Background. Meniscus repair can restore the function of torn meniscus in anterior cruciate ligament (ACL)-reconstructed knees. However, few reports investigate the relationship between concurrent meniscus repair with ACL reconstruction and postoperative meniscal position. This study aimed to evaluate the size of the medial meniscus in patients who underwent ACL reconstruction and concomitant all-inside medial meniscus repair. Methods. This study received the approval of our Institutional Review Board. Twenty patients underwent ACL reconstruction and concurrent medial meniscus repair of a peripheral longitudinal tear using the FasT-Fix meniscal repair device. Medial tibial plateau length (MTPL) and width (MTPW) were determined by radiographic images. We evaluated the Lysholm score, anteroposterior instability (difference in KT-2000 arthrometer measurement), meniscal healing, and magnetic resonance imaging (MRI)-based medial meniscal length (MML) and width (MMW). The healing status of repaired medial meniscus was assessed by 2nd-look arthroscopy. Results. ACL reconstruction improved the Lysholm score and anteroposterior instability. All the patients showed complete healing of the repaired meniscus in 2nd-look arthroscopic evaluation. Significant increase of MML and MML percentage (100 × MML/MTPL) was observed after concurrent all-inside medial meniscus repair with ACL reconstruction. However, MMW and MMW percentage (100 × MMW/MTPW) were not affected. Conclusions. Concurrent all-inside medial meniscus repair with ACL reconstruction had satisfactory clinical results. Anteroposterior length of the medial meniscus increased after surgery. Our results suggest that medial meniscus repair associated with ACL reconstruction may affect the biomechanical function of the medial meniscus. Level of Evidence. Case-control study, Level IV. Disclosure. The authors have no conflicts of interest

Summary. Our statistical shape analysis showed that size is the primary geometrical variation factor in the medial meniscus. Shape variations are primarily focused in the posterior horn, suggesting that these variations could influence cartilage contact pressures. Introduction. Variations in meniscal geometry are known to influence stresses and strains inside the meniscus and the articulating cartilage surfaces. This geometry-dependent functioning emphasizes that understanding the natural variation in meniscus geometry is essential for a correct selection of allograft menisci and even more crucial for the definition of different sizes for synthetic meniscal implants. Moreover, the design of such implants requires a description of 3D meniscus geometry. Therefore, the aim of this study was to quantify 3D meniscus geometry and to determine whether variation in medial meniscus geometry is size or shape driven. Patients & Methods. Sagittal knee MR images (n=35; 15 males, 20 females, aged 33±12) were acquired at 3 Tesla using a 3D SPACE sequence with isotropic resolution of 0.5×0.5×0.5mm. 3D models were generated by manual segmentation of the medial menisci from the MR scans. The surface of a reference meniscus was then described by 250 landmarks. Using an affine iterative closest point transformation, these landmarks were registered onto the full set of 3D models. Based on the set of corresponding landmarks, a point distribution model was created using the Shapeworks software (NITRC, University of Utah), an open source algorithm for constructing correspondence-based statistical models of sets of similar shapes. Several modules from Shapeworks and the Arthron software (UCD, Dublin) were used to perform principal component analysis (PCA) upon the set of landmarks. The results of the PCA enabled quantification and visualisation of the primary modes of variation in meniscal geometry. Results. The majority (77%) of variation in medial meniscus geometry was found to be due to sizing (principal component (PC) 1). Including the shape-related PC's 2 to 4, increased the cumulative percentage of represented geometry variation to over 90%. The independent shape variations described by PCs 2–4 all display larger variations in geometry of the posterior meniscal horn than the anterior section. Discussion. From this study, we can conclude that geometry variation of the medial meniscus is mainly determined by differences in size. However, since the posterior aspect of the medial meniscus experiences higher loads during daily activities than the anterior part, the shape variations described by PCs 2–4 may have a significant influence on cartilage contact pressures. Therefore, PCA alone does not provide sufficient information to define the number of implant sizes to cover a majority of the population. Analysis of the sensitivity of cartilage contact pressures to the shape variations identified in this analysis could provide the additional information needed

Introduction. Post-meniscectomy syndrome is broadly characterised by intractable pain following the partial or total removal of a meniscus. There is a large treatment gap between the first knee pain after meniscectomy and the eligibility for a TKA. Hence, there is a strong unmet need for a solution that will relieve this post-meniscectomy pain. Goal of this first-in-man study was to evaluate the safety and performance of an anatomically shaped artificial medial meniscus prosthesis and the accompanying surgical technique. Methods. A first-in-man, prospective, multi-centre, single arm clinical investigation was intended to be performed on 18 post-medial meniscectomy syndrome patients with limited underlying cartilage damage (Kellgren Lawrence scale 0–3) in the medial compartment and having a normal lateral compartment. Eventually 5 patients received a polycarbonate urethane mediale meniscus prosthesis (Trammpolin® medial meniscus prosthesis; ATRO Medical B.V., the Netherlands) which was clicked onto two titanium screws fixated at the native horn attachments on the tibia. PROMs were collected at baseline and at 6 weeks, 3, 6, 12 and 24 months following the intervention including X-rays at 6, 12 and 24 Months. MRI scans were repeated after 12 and 24 months. Results. The surgical technique to select the appropriately sized implant and correct positioning of the fixation screws and meniscus prosthesis onto the tibia was demonstrated feasible and reproducible. The surgeries showed that in particular the positioning of the posterior screw is crucial for correct positioning of the prosthesis. Inclusion stopped after 5 patients, who reached the 6 months evaluation. The PROMs did not improve in the first 6 months after surgery. All patients reported knee joint stiffness and slight effusion in their knee at 6 months follow-up. In case of symptomatic patients an evaluation of the device position and integrity was performed by MRI. In three patients the implants were removed because of implant failure and in one patient the implant was removed because of persistent pain and extension deficit. At present one patient has the implant still in situ. The explantations of the implants demonstrated no articular cartilage damage and the fixation screws were securely anchored. Discussion. This is the first clinical study with an artificial meniscus-like prosthesis. Except one, all implants were removed due to implant breakage or discomfort of the patient. Analysis of the torn implants showed fatigue failure resulting from the lack of loadsharing between implant and cartilage: the implant was too stiff and carried all the load in the medial compartment of the knee. Furthermore, the fixation with screws seemed too rigid which restricted the motion of the posterior horn. Based on previous in vitro and animal experiments, we expected more creep of the material and more motion on the screw fixation. Conclusion. This first-in-man clinical study demonstrates that the investigated device design is not safe and did not perform as expected. Therefore, modification of the meniscus prosthesis design and fixation technique is required to allow for more motion of the meniscus prosthesis during knee joint movement

Introduction. The major function of the medial meniscus has been shown to be distribution of the load with reduction of cartilage stresses, while its role in AP stability has been found to be secondary. However several recent studies have shown that cartilage loss in OA occurs in the central region of the tibia while the meniscus is displaced medially. In a lab study (Arno, Hadley 2013) it was confirmed that the AP laxity was greatly reduced with a compressive force across the knee, while the femur shifted posteriorly and the AP laxity was increased after a partial meniscetomy of the posterior horn. It is therefore possible that under load, the compression of the meniscus and the cartilage, 2–3mm in total, allows load transmission on the central tibial plateau, and causes radial expansion and tension of the meniscus providing restraint to femoral displacements. This leads to our hypotheses that the highest loading on the medial meniscus would be at the extremes of motion, rather than in the mid-range, and that the meniscus would provide the majority of the restraint to anterior-posterior femoral displacements throughout flexion when compressive loads were acting. Methods & Materials. MRI scans were taken of ten knee specimens to verify the absence of pathology and produce computer models. The knees were loaded in combinations of compressive and shear loading over a full flexion range. Tekscan sensors were used to measure the pressure distribution across the joint as the knee was flexed continuously. A digital camera was used to track the motion, from which femoral-tibial contacts were determined by computer modelling. Load transmission was determined from the Tekscan for the anterior horn, central body, posterior horn, and the uncovered cartilage in the center of the meniscus. An analysis was carried out (Fig 2) to determine the net anterior or posterior shear force carried by the meniscus. Results. For the three types of loading (Fig 1); compression only, compression and anterior shear, compression and posterior shear; between 40–80% of the total load was transmitted through the meniscus, the overall average being 58%. The remaining 42% was transmitted directly through the uncovered cartilage. The anterior horn was loaded only up to 30 degrees flexion, and played a role in controlling anterior femoral displacement. The central body was loaded 10–20% and would provide some restraint to medial femoral subluxation. Overall the posterior horn carried the highest percentage of the shear load (Figure 3), especially after 30 degrees flexion when a posterior shear force was applied, for which the meniscus was estimated to carry 50% of the shear force. Discussion. The hypotheses were largely supported. There was high anterior horn loading in early flexion, but in the remaining range, the posterior horn was the highest loaded especially under posterior shear. Supporting the posterior shear force under load bearing conditions is evidently an important role of the meniscus. Hence in any attempts at repair or replacement, these dual functions of load-sharing and stability need to be incorporated

Introduction Magnetic resonance imaging (MRI) is important in non-invasive evaluation of osseous and soft-tissue structures in the post-traumatic knee. However, it is sometimes impossible to determine if a focus of high signal intensity in the meniscus is confined to the substance, or extends to involve the joint surface. This is a critical differentiation as the latter represents menisci tears that can be found and treated arthroscopically, whereas the former represents degradation, intra-substance tears or normal variants not amenable to arthroscopic intervention. The aim of this study was to investigate occurrence of altered signal intensity in the posterior horn of the medial meniscus and correlate with arthroscopic findings. Materials and Methods 64 patients with suspected post-traumatic internal derangement of the knee who underwent MRI prior to arthroscopy were evaluated. All patients initially had MR imaging of the symptomatic knee using a standard protocol in a Siemens Symphony 1.5 Tesle Magnetom. MR images were then interpreted and reported by 2 radiologists experienced in MR and skeletal radiology. Meniscal tears were graded according to the system validated by Lotysch. A Grade 3 signal was considered unequivocal evidence of a meniscal tear. Equivocal tears (Grade 2/3 signal) were diagnosed if it was unclear if there was a small portion of normal intact meniscal tissue between a linear high signal in the meniscus and the articular surface abutting the meniscus. Arthroscopy was subsequently performed by senior surgeons aware of the MR findings within 2 weeks of imaging. Patients were re-assessed clinically and evaluated functionally at a mean follow-up time of 5 months. Radiographic, arthroscopic and clinical results were then correlated and evaluated. Results There were 48 males and 16 females in the group, with a mean age of 28.2 years.. Tears of the posterior horn of the medial meniscus were reported on MRI unequivocally (Grade 3 signal) in 18 patients and equivocally (Grade 2/3 signal) in 10 patients. Subsequent arthroscopic correlation revealed 16 tears (89%) in the unequivocal group and only one tear (10%) in the equivocal group. Discusion The finding that only 10% of patients with an equivocal tear in the posterior horn of the medial meniscus on MRI were subsequently found to have a tear on arthroscopy would suggest that early arthroscopic intervention is not warranted in these cases. We suggest that unless symptoms persist over the course of 3 to 6 months, or if a more compelling symptom complex develops, only then should arthroscopic evaluation be considered. Conclusion Equivocal tears on MRI of the posterior horn of the medial meniscus have a low rate of arthroscopically detected tears and a trial of conservative therapy may be prudent in such cases

The aim of this work was to develop a novel, accessible and low-cost method, which is sufficient to measure changes in meniscal position in a whole-knee joint model performing dynamic motion in a knee simulator. An optical tracking method using motion markers, MATLAB (MATLAB, The MathWorks Inc.) and a miniature camera system (Raspberry Pi, UK) was developed. Method feasibility was assessed on porcine whole joint knee samples (n = 4) dissected and cemented to be used in the simulator (1). Markers were placed on three regions (medial, posterior, anterior) of the medial meniscus with corresponding reference markers on the tibial plateau, so the relative meniscal position could be calculated. The Leeds high kinematics gait profile scaled to the parameters of a pig (1, 2) was driven in displacement control at 0.5 Hz. Videos were recorded at cycle-3 and cycle-50. Conditions tested were the capsule retained (intact), capsule removed and a medial posterior root tear. Mean relative displacement values were taken at time-points relating to the peaks of the axial force and flexion-extension gait inputs, as well as the range between the maximum and minimum values. A one-way ANOVA followed by Tukey post hoc analysis were used to assess differences (p = 0.05). The method was able to measure relative meniscal displacement for all three meniscal regions. The medial region showed the greatest difference between the conditions. A significant increase (p < 0.05) for the root tear condition was found at 0.28s and 0.90s (axial load peaks) during cycle-3. Mean relative displacement for the root tear condition decreased by 0.29 mm between cycle-3 and cycle-50 at the 0.28s time-point. No statistically significant differences were found when ranges were compared at cycle-3 and cycle-50. The method was sensitive to measure a substantial difference in medial-lateral relative displacement between an intact and a torn state. Meniscus extrusion was detected for the root tear condition throughout test duration. Further work will progress onto human specimens and apply an intervention condition

Altered mechanical loading is a widely suggested, but poorly understood potential cause of cartilage degeneration in osteoarthritis. In rodents, osteoarthritis is induced following destabilization of the medial meniscus (DMM). This study estimates knee kinematics and contact forces in rats with DMM to gain better insight into the specific mechanisms underlying disease development in this widely-used model. Unilateral knee surgery was performed in adult male Sprague-Dawley rats (n=5 with DMM, n=5 with sham surgery). Radio-opaque beads were implanted on their femur and tibia. 8 weeks following knee surgery, rat gait was recorded using the 3D²YMOX setup (Sanctorum et al. 2019, simultaneous acquisition of biplanar XRay videos and ground reaction forces). 10 trials (1 per rat) were calibrated and processed in XMALab (Knörlein et al. 2016). Hindlimb bony landmarks were labeled on the XRay videos using transfer learning (Deeplabcut, Mathis et al. 2019; Laurence-Chasen et al. 2020). A generic OpenSim musculoskeletal model of the rat hindlimb (Johnson et al. 2008) was adapted to include a 3-degree-of-freedom knee. Inverse kinematics, inverse dynamics, static optimization of muscle forces, and joint reaction analysis were performed. In rats with DMM, knee adduction was lower compared to sham surgery. Ground reaction forces were less variable with DMM, resulting in less variability in joint external moments. The mediolateral ground reaction force was lower, resulting in lower hip adduction moment, thus less force was produced by the rectus femoris. Rats with DMM tended to break rather than propel, resulting in lower hip flexion moment, thus less force was produced by the semimembranosus. These results are consistent with lower knee contact forces in the anteroposterior and axial directions. These preliminary data indicate no overloading of the knee joint in rats with DMM, compared with sham surgery. We are currently expanding our workflow to finite element analysis, to examine mechanical cues in the cartilage of these rats (Fig1G)

Magnetic resonance imaging has emerged as an important modality in the non-invasive evaluation of osseous and soft-tissue structures in the post-traumatic knee. However, it is sometimes radiologically impossible to determine with confidence if a focus of high signal intensity in the meniscus is confined to the substance of the meniscus or if it extends to involve the joint surface. This is a critical differentiation because the latter represents menisci tears that can be found and treated arthroscopically, whereas the former represents degradation, intrasubstance tears or perhaps normal variants that are not amenable to arthroscopic intervention. The aim of this study was to investigate the occurrence of altered signal intensity in the posterior horn of the medial meniscus in correlation with arthroscopic findings. Sixty-four patients with suspected post-traumatic internal derangement of the knee who underwent magnetic resonance imaging prior to arthroscopy were evaluated retrospectively. There were 48 males and 16 females. Mean age was 28.2 years. Tears of the posterior horn of the medial meniscus were diagnosed unequivocally (Grade 3 signal) in 18 patients and equivocally (Grade 2/3 signal) in 10 patients. Arthroscopic correlation revealed 16 tears (89%) in the unequivocal group and only one tear (10%) in the equivocal group). A meniscal tear is unlikely when magnetic resonance imaging shows a focus of high signal intensity in the posterior horn of the medial meniscus that does not unequivocally extend to involve the inferior or superior joint surface. An appropriate trial of non-operative treatment is recommended in such questionable cases. Magnetic resonance imaging is a useful diagnostic tool, however, it should be used selectively, and in conjunction with history and clinical examination in evaluating internal derangement of the knee

The meniscus is a fibrocartilaginous tissue that plays an important role in controlling the complex biomechanics of the knee. Many histological and mechanical studies about meniscal attachment have been carried out, and medial meniscus (MM) root repair is recommended to prevent subsequent cartilage degeneration following MM posterior root tear. However, there are only few studies about the differences between meniscus root and horn cells. The goal of this study was to clarify the differences between these two cells. Tissue samples were obtained from the medial knee compartments of 10 patients with osteoarthritis who underwent total knee arthroplasty. Morphology, distribution, and proliferation of MM root and horn cells, as well as gene and protein expression levels of Sry-type HMG box (SOX) 9 and type II collagen (COL2A1) were determined after cyclic tensile strain (CTS) treatment. Horn cells had a triangular morphology, whereas root cells were fibroblast-like. The number of horn cells positive for SOX9 and COL2A1 was considerably higher than that of root cells. Although root and horn cells showed similar levels of proliferation after 48, 72, or 96 h of culture, more horn cells than root cells were lost following 2-h CTS (5% and 10% strain). SOX9 and COL2A1 mRNA expression levels were significantly enhanced in horn cells compared with those in root cells after 2- and 4-h CTS (5%) treatment. This study demonstrates that MM root and horn cells have distinct characteristics and show different cellular phenotypes. Our results suggest that physiological tensile strain is important for activating extracellular matrix production in horn cells. Restoring physiological mechanical stress may be useful for promoting healing of the MM posterior horn

In 20 skeletally mature female merino sheep, divided into four groups, we performed total medial meniscectomy, removal of the middle third of the patellar tendon, and tenotomy of the calcaneal tendon of the right hind leg. Group I (control) had no additional procedures. In the other three groups the medial meniscus was replaced by the middle third of the patellar tendon from the ipsilateral knee. The animals were killed at three (group II), six (group III), or 12 months (group IV) and the tendon-meniscus examined macroscopically, by light and scanning electron microscopy, and biomechanically. Remodelling of the tissue had taken place by 12 months but the failure stress and tensile modulus for the tendon-meniscus were lower than for the normal meniscus. Our evidence suggests that, in sheep, replacement of a meniscus by a tendon autograft may decrease the severity of the degenerative changes that occur after meniscectomy

Purpose of the study: One of the most frequent complications of medial meniscal suture is injury to the saphenous nerve or its branches. The purpose of this study was to ascertain the relations of the medial meniscus with the infrapatellar branches of the saphenous nerve. Material and methods: Twenty lower limbs were dissected to study the pathways of the saphenous nerve and its branches in relation to different landmarks of the medial meniscus and palpable bony zones. Sixteen measurements were made on each knee held in extension. Results: The infrapatellar trunk of the saphenous nerve exhibited two terminal branches in all knees dissected. Level of the bifurcation in relation to the joint space varied. Similarly the position of the branches varied greatly in relation to different landmarks. The most frequent configuration was a main trunk situated 8 mm anteriorly to the tubercle of the great adductor and 60 mm from the mid point of the medial border of the patella. The bifurcation into two branches was situated 23 mm above the joint space. The two branches ran obliquely anteriorly and inferiorly forming an angle of 55° on average with a vertical line. The superior branch ran 24 mm behind the anterior meniscal point and 55 mm from the posterior meniscal point; the inferior branch ran 42.6 mm and 38 mm from these two points. Discussion: Injury to the saphenous nerve or its branches is mainly observed for suturing techniques done medially to laterally. Incidence has reached 38% in certain series. This incidence has declined with the increasingly widespread use of arthroscopy, but saphenous injury still occurs for meniscal repairs using a posteromedial approach. The risk is similar for medially to laterally or laterally to medially sutures. Since there is no safety zone, it would be advisable to prefer an «all medially» technique. Conclusion: Measurements made on dissection specimens enabled us to delimit three zones of increasing risk for nerve injury. The zone with the highest risk measures 20 mm wide. Its anterior limit is situated behind the most anterior meniscal point and its posterior limit is situated 28 mm from the posterior meniscal point

Although osteoarthritis (OA) is characterized by articular cartilage damage, synovial inflammation is a prominent feature contributing to disease progression. In addition to synovial tissue resident macrophages, infiltrating macrophages and monocytes, their lineage precursors, may also contribute to pathological processes. In mice, peripheral blood monocytes may be categorized according to pro-inflammatory/classical and patrolling/non-classical subsets. The aim of this study was to identify profiles of peripheral blood monocyte subsets as well as different synovial macrophage phenotypes during disease development. OA was induced in knees of C57BL/6 mice by destabilization of the medial meniscus (DMM). Blood was harvested from the facial vein 7 days prior to and 1, 7, 14, 28, and 56 days post induction of OA. Separate mice were sham-operated as a control. Monocyte subsets and synovial macrophage populations were identified by flow cytometry. Levels of classical monocytes were significantly higher at day 14 (p<0.001) and day 28 (p=0.031) in peripheral blood of DMM-operated mice compared to control. Furthermore, the percentage of non-classical monocytes was significantly lower in DMM-mice at day 14 (p=0.026). At day 56 post OA-induction, an increase in total synovial macrophages (CD11b+F4/80+ cells) was observed between DMM and sham operated knees (p=0.021). The ratio between pro-inflammatory (CD11b+F4/80+CD86+) and tissue repair (CD11b+F4/80+CD206+) synovial macrophage subsets tended to be higher in DMM knees, however this finding was not statistically significant (p>0.05). In light of the present findings, further investigation is required to elucidate the relationship of peripheral blood monocyte subsets to synovial inflammation and features of OA pathogenesis

Aims. To fully quantify the effect of posterior tibial slope (PTS) angles on joint kinematics and contact mechanics of intact and anterior cruciate ligament-deficient (ACLD) knees during the gait cycle. Methods. In this controlled laboratory study, we developed an original multiscale subject-specific finite element musculoskeletal framework model and integrated it with the tibiofemoral and patellofemoral joints with high-fidelity joint motion representations, to investigate the effects of 2.5° increases in PTS angles on joint dynamics and contact mechanics during the gait cycle. Results. The ACL tensile force in the intact knee was significantly affected with increasing PTS angle. Considerable differences were observed in kinematics and initial posterior femoral translation between the intact and ACLD joints as the PTS angles increased by more than 2.5° (beyond 11.4°). Additionally, a higher contact stress was detected in the peripheral posterior horn areas of the menisci with increasing PTS angle during the gait cycle. The maximum tensile force on the horn of the medial meniscus increased from 73.9 N to 172.4 N in the ACLD joint with increasing PTS angles. Conclusion. Knee joint instability and larger loading on the medial meniscus were found on the ACLD knee even at a 2.5° increase in PTS angle (larger than 11.4°). Our biomechanical findings support recent clinical evidence of a high risk of failure of ACL reconstruction with steeper PTS and the necessity of ACL reconstruction, which would prevent meniscus tear and thus the development or progression of osteoarthritis. Cite this article: Bone Joint Res 2022;11(10):739–750

Introduction: Instability of the anterior horn of the medial meniscus (MM) has been described as dislocating, subluxating or hypermobile, but it is still controversial whether segments of the MM of the knee were surgically treated by arthroscopic stabilization. The average age of the patients was 28.7 (range 12 to 56). There were 9 men and 4 women. All patients complained of medial knee pain and felt tenderness in the medial joint space, most of them on the anterior side. None showed an apparent tear of the meniscus by arthroscopy or on MRI images, but all arthroscopically showed hypermobility (or easy dislocation from the edge of the tibial plateau) of the anterior to middle segment of the MM. No other apparent pathological changes were found. Six knees had marked limitations in the range of knee motion before operation. Arthroscopic stabilization of the hypermobility was performed in order to restrain the movement of the MM by fixing it to the tibial edge, using staples (2 cases), Kirschner wires (2 cases) or suture anchors (9 cases). Using the Japanese Orthopaedic Association meniscus injury score (maximum 100 points), the result was evaluated. The average follow up period was 20.1 months (range 9 to 49 months). Results: The result of arthroscopic fixation was satisfactory (excellent in 8 cases good in 1, fair in 1, and poor in 1). The average meniscus score at follow up was 87.8, while that of before operation was 41.9. It is suggested that instability of the anterior segment of the MM can be effectively treated by arthroscopic fixation of this site. Discussion: Since all of the knees in this study had an isolated lesion of instability in the anterior segment of the MM, the marked improvement in medial knee pain that resulted from fixation of this site does show that this lesion can be symptomatic. After excluding other possible pathological lesions, stabilization of this lesion by arthroscopic fixation is a good choice of treatment

Purpose: The collagen meniscus implant (CMI, Sulzer) is a meniscal substitute with a collagen matrix serving as a tutor for autologous regeneration of meniscal tissue. The goal is to prevent mid-term degradation after meniscectomy. The CMI is inserted arthroscopically. The purpose of this multicentric European study was to verify the safety, technical feasibility, and short-term clinical efficacy of the CMI in a population of patients undergoing medial meniscectomy. The long-term results should be obtained within a delay of five years at least. Material and results: The series included patients with medial meniscus lesions alone, with or without lesions of the anterior cruciate ligament (present in 44% of the patients and repaired at the same time). Patient consent was obtained in all cases (in France in accordance with the Huriet law). Patients with lesions of the lateral ligament, associated trade IV cartilage lesions, or lesions of the posterior cruciate ligament were excluded. The study included 98 patients, mean age 33 years. Four patients were excluded from the analysis due to complications. Currently, 66 patients are available for evaluation one year after insertion of the CMI. Subjective outcome, the Lysholm score, and x-ray and MRI findings were recorded. Evaluation up to five years follow-up is scheduled. Results: Complications: There were four early complications: infectious arthritis (n=1), puriform arthritis without germ (n=2), implant rupture (n=1). There were no implant-related postop complications. Clinical results: At one year follow-up, the Lysholm score was 97. Pain was mild (1 on the visual analogue scale) and was only observed in one out of six patients: 87% of the patients had a normal or nearly normal knee. Radiological results: There were no radiological signs of early degeneration. It was difficult to interpret the MRI results which visualised a structure with an intermediary signal in the form of a meniscal triangle. MRI did on show any sign of deleterious effect on the neighbouring cartilage. Discussion: This technique for replacing the meniscus is an alternative to allogenic grafting. These preliminary results must of course be interpreted with caution. They show that arthroscoic implantation of the CMI is feasible but difficult. There was no evidence of an immunological reaction. Complications were related to the operative difficulty. Clinical results were satisfactory at one year, particularly in terms of pain. On the other hand, the biomechanical value of the implant cannot be assessed until longer follow-up data becomes available. Conclusion: In light of the operative difficulty, the long postoperative recovery due to the rehabilitation protocol, the CMI should be used for symptomatic knees after meniscectomy, particularly in case of anterior laxity

We report the clinical and arthroscopic findings in 20 cases of medial meniscal cyst with a mean follow-up of 20 months. These were studied prospectively from a series of 7435 knee arthroscopies in which there were 1246 stable non-arthritic knees with medial meniscal tears. The diagnosis on referral was incorrect in seven, and incomplete in seven. There was coexistent meniscal injury in 17 (85%), but in the other three no tear was visible at arthroscopy. Ten knees had additional intra-articular abnormalities. Treatment of the cyst was by open resection in 12 and arthroscopic evaluation at meniscectomy in seven. In one case the cyst resolved after arthroscopic partial meniscectomy alone. Meniscal tears were treated by arthroscopic partial medial meniscectomy. Medial meniscal cysts are an important but under-diagnosed cause of knee pain and are frequently related to arthroscopically diagnosable and treatable meniscal pathology. Treatment should be directed towards both the meniscus and the cyst, which may require open surgery.

Purpouse. We hypothesized that patients receiving a medial collagen meniscus implant (MCMI) would show better clinical, radiograpich and Magnetic Resonanace Imaging (MRI) outcomes than patients treated with partial medial meniscectomy (PMM) at minimum 10 year FU. Material and Methods. Thirty-three non-randomized patients (males, mean age 40 years) were enrolled in the study to receive a MCMI (17 patients) or as control treated with a PMM (16 patients). All of them were clinically evaluated at time zero, 5 and minimum 10 years after surgery (mean FU 133 months, range 120–145) by Lysholm, VAS for pain, objective IKDC knee form and Tegner activity level. SF-36 score was performed pre-operatively and at final FU. Bilateral weight-bearing XRays were executed at time zero and at final FU. Minimum 10 years FU MRI images were compared with collected pre-operative MRI images by means of Yulish score. Genovese score was also used to evalute MCMI MRI survivorship. Results. MCMI group showed significantly lower VAS for pain (p = 0.0091), higher objective IKDC (p = 0.0026), Teger index (p = 0.0259) and SF-36 (p = 0.0259 for PHI and p = 0.0036 for MHI) scores compared with PMM group at minimum 10 year FU. Radiographic evaluation showed a significantly lower medial joint line height (p = 0.0002) and side-to-side difference (p = 0.0003) narrowing in MCMI group respect to PMM group at final FU. Discussion. Improvements in pain relief, activity level, objective IKDC score and joint-line preservation are detectable with the use of MCMI at a minimum 10 year FU. On the authors knowledge this is the first long-term controlled trial regarding this device, and our findings confirmed the mid-term good results achieved by Rodkey et al (1). Conclusions. This data support the use of meniscal scaffolds to treat irreparable partial meniscal lesions. Long-term prospective randomized controlled trials on a larger population are necessary to determine the extent and duration of the benefits observed

Meniscal tears commonly co-occur with ACL tears, and many studies address their side, pattern, and distribution. Few studies assess the patient's short-term functional outcome concerning tear radial and circumferential distribution based on the Cooper et al. classification. Meniscal tears require primary adequate treatment to restore knee function. Our hypothesis is to preserve the meniscal rim as much as possible to maintain the load-bearing capacity of the menisci after meniscectomy. The purpose of this study is to document the location and type of meniscal tears that accompany anterior cruciate ligament (ACL) tears and their effect on patient functional outcomes following arthroscopic ACL reconstruction and meniscectomy. This prospective cross-sectional observational study was conducted at AL-BASRA Teaching Hospital in Iraq between July 2018 and January 2020 among patients with combined ipsilateral ACL injury and meniscal tears. A total of 28 active young male patients, aged 18 to 42 years, were included. All patients were subjected to our questionnaire, full history, systemic and regional examination, laboratory investigations, imaging studies, preoperative rehabilitation, and were followed by Lysholm score 6 months postoperatively. All 28 patients were males, with a mean age of 27 ± 0.14 years. The right knee was the most commonly affected in 20/28 patients (71.4%). The medial meniscus was most commonly injured in 11 patients, 7 patients had lateral meniscal tears, and 10 patients had tears in both menisci. The most common tear pattern of the medial meniscus was a bucket handle tear (36.4%), while longitudinal tears were the most frequent in the lateral meniscus (71.4%) (P-value = 0.04). The most common radial tear location was zone E-F (5/28, 17.8%), and the most common circumferential zone affected was the middle and inner third, reported in 50% of tears. Good and excellent outcomes using the Lysholm score after 6 months were obtained in 42.9% and 17.9% of patients, respectively. Better functional scores were associated with lateral meniscal tears, bucket handle tears, tears extending to a more peripheral vascular area, and if no more than one-third of the meniscus was resected (P-value = 0.002). Less favourable outcomes were reported in smokers, posterior horn tears, and when surgery was delayed more than 1 year (P-value = 0.03). We conclude that there is a negative correlation between the amount of meniscus resected and functional outcome. Delayed ACL reconstruction increases the risk of bimeniscal tears. Bucket handle tears are the most common tears, mostly in the medial meniscus, while longitudinal tears are most common in the lateral meniscus. We recommend performing early ACL reconstruction within 12 months to reduce the risk of bimeniscal injuries

Aims. Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods. In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results. DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion. We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273

Aims. Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. Methods. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. Results. In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. Conclusion. Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA. Cite this article: Bone Joint Res 2023;12(2):121–132

Aims. Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2. -/-. ) display accelerated bone growth. Methods. We examined vulnerability of Socs2. -/-. mice to OA following surgical induction of disease (destabilization of the medial meniscus (DMM)), and with ageing, by histology and micro-CT. Results. We observed a significant increase in mean number (wild-type (WT) DMM: 532 (SD 56); WT sham: 495 (SD 45); knockout (KO) DMM: 169 (SD 49); KO sham: 187 (SD 56); p < 0.001) and density (WT DMM: 2.2 (SD 0.9); WT sham: 1.2 (SD 0.5); KO DMM: 13.0 (SD 0.5); KO sham: 14.4 (SD 0.7)) of growth plate bridges in Socs2. -/-. in comparison with WT. Histological examination of WT and Socs2. -/-. knees revealed articular cartilage damage with DMM in comparison to sham. Articular cartilage lesion severity scores (mean and maximum) were similar in WT and Socs2. -/-. mice with either DMM, or with ageing. Micro-CT analysis revealed significant decreases in SCB thickness, epiphyseal trabecular number, and thickness in the medial compartment of Socs2. -/-. , in comparison with WT (p < 0.001). DMM had no effect on the SCB thickness in comparison with sham in either genotype. Conclusion. Together, these data suggest that enhanced GH signalling through SOCS2 deletion accelerates growth plate fusion, however this has no effect on OA vulnerability in this model. Cite this article: Bone Joint Res 2022;11(3):162–170

Aims. Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear. Methods. In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. Results. The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Conclusion. Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA. Cite this article: Bone Joint Res 2024;13(3):110–123

Aims. Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis. Methods. Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression. Results. Tensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively ‘sponging’ miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice. Conclusion. Taken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA. Cite this article: Bone Joint Res 2023;12(1):33–45

Aims. Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive. Methods. A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed. Results. Eight-week treadmill-walking was effective at maintaining the integrity of cartilage-subchondral bone unit and reducing the elevated systematic inflammation factors and microbiome-derived metabolites. Furthermore, 16S ribosomal ribonucleic acid (rRNA) sequencing showed disease-relevant microbial shifts in PTOA animals, characterized by the decreased abundance of phylum TM7 and the increase of phylum Fusobacteria. At the genus level, the abundance of Lactobacillus, Turicibacter, Adlercreutzia, and Cetobacterium were increased in the PTOA animals, while the increase of Adlercreutzia and Cetobacterium was weakened as a response to exercise. The correlation analysis showed that genus Lactobacillus and Adlercreutzia were correlated to the structural OA phenotypes, while phylum Fusobacteria and genus Cetobacterium may contribute to the effects of exercise on the diminishment of serological inflammatory factors. Conclusion. Exercise is effective at maintaining the integrity of cartilage-subchondral bone unit, and the exercise-induced modification of disease-relevant microbial shifts is potentially involved in the mechanisms of exercise-induced amelioration of PTOA. Cite this article: Bone Joint Res 2022;11(4):214–225

Aims. Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. Methods. OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot. Results. Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1β-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro. Conclusion. Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: Bone Joint Res 2021;10(11):704–713

Aims. MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms. Methods. Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG. Results. miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines (IL-6, IL-1β, TNF-α) and pain-related factors (TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα. Conclusion. Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα-CCL2/CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548–557

Introduction. Most of the algorithm available today to balance varus knee is based on a surgeon's hands-on experience without full understanding of pathological anatomy of varus knee. The high-resolution MRI allows us to recognize the anatomical details of the posteromedial corner and the changes of the soft tissue associated with the osteoarthritis and varus deformity. We have in this study, reviewed 60 cases of severe varus knee scheduled for TKR and compared it to normal MRI and those MRI were evaluated and read by a musculoskeletal radiologist. We have documented clearly the changes that happens in soft tissue, leading to tight medial compartment. We will also show multiple short intra-operative video confirming that MRI findings. Material & method. We have retrospectively reviewed the MRI on 60 patients with advanced osteoarthritis varus knee. We also reviewed 20 MRI for a normal knee matched for age. We evaluated the posteromedial complex and MCL in sagittal PD-weighted VISTA to check the alignment of the MCL and posteromedial complex and the associate MCL bowing and deformity that could happen in osteoarthritis knee. We have measured the thickness of the posteromedial complex and the posterior medial bowing of the superficial MCL and the involvement of the posterior oblique ligament in those patients. To measure the posterior bowing of the MCL, a line was drawn through the posterior aspect of both menisci and we measured the distance between the posterior edge of MCL to that line in actual image. To measure the thickness of the posteromedial complex, we measured it at two areas in the posterior medial corner posteriorly at the level of the medial meniscus. Measuring the medial bowing of the MCL was done by a line drawn through the medial edge of the femoral condyle and the tibial condyle at the level of the medial meniscus to the inner aspect of the MCL. The normal distance between the posterior aspects of the MCL to the posterior meniscus line was approximately measured 2 cm. in average. Results. We were able to recognize and measure the medial deviation of MCL in all arthritic knees due to the deformity and the effect of the medial margin osteophyte and medial extrusion of the meniscus. Thickening of posteromedial complex was recognized in the majority of the cases with prominent thickening seen in 50/60 knees with average thickness measuring approximately 1.2 cm due to the synovial thickening, adhesions, granulation tissue, degenerated medial meniscus, and involvement of the posterior oblique ligament and the capsular branch of the semimembranosus tendon, as well as the oblique popliteal ligament. The involvement of posterior oblique ligament were seen in majority of the cases. In 55 cases we have showed a heterogeneous appearance of the ligament and loss of normal signal within the postero medial complex and we have documented that the oblique ligament will cause the posterior bowing of the MCL. The medial bowing of the MCL is also correlated to the severity of the varus deformity with an average distance to the normal medial line of the medial meniscus measuring approximately 1.1 cm. Discussion. Our study shows that the changes affecting the superficial MCL is likely to be secondary to the obvious changes involving the posteromedial complex and to the marginal osteophyte as well as the extrusion of the medial meniscus. Also, we have confirmed that there are deforming structures such as the oblique ligament with adhesion and thickening with all the posterior medial complex. Those changes clearly caused the posterior bowing to the superficial MCL without an actual shortening of the ligament. The scarring tissue in the posteromedial corner and the adhesion is acting as a soft phyte tensioning and deforming the ligament and the posterior capsule. The oblique ligament act as a deforming forces forcing the superficial MCL to bow posteriorly. The lengths of the superficial MCL stayed the same. Conclusion. The conventional wisdom of releasing the distal attachment of the superficial medial MCL to balance knee has to be a challenge based on our MRI finding. Releasing the superficial MCL can sometimes lead to a major instability of the knee requiring a more constrained implant. Our MRI assessment clearly showed that the Superficial MCL is deformed because of posterior bowing and medial bowing and considerable thickening of the posteromedial corner, as well as the accompanying osteophyte. We believe that clearing the superficial MCL and excising those thickened scar tissue in the posterior medial corner will enable us to balance the knee without creating instability Conclusion: The conventional wisdom of releasing the distal attachment of the superficial medial MCL to balance knee has to be a challenge based on our MRI finding. Releasing the superficial MCL can sometimes lead to a major instability of the knee requiring a more constrained implant. Our MRI assessment clearly showed that the Superficial MCL is deformed because of posterior bowing and medial bowing and considerable thickening of the posteromedial corner, as well as the accompanying osteophyte. We believe that clearing the superficial MCL and excising those thickened scar tissue in the posterior medial corner will enable us to balance the knee without creating instability

Recent findings have identified the importance of previously undiagnosed or neglected meniscus lesions in association with anterior cruciate ligament (ACL) injuries (e.g. medial meniscus ramp lesions and posterior root tears of the lateral meniscus). There is increasing biomechanical evidence that they bear the potential to alter both anteroposterior and rotational laxity patterns in ACL injured knees. Few data exist with respect to the presence of these specific tear entities in large series of ACL injured patients. The purpose of the study was to analyze the meniscus tear pattern in a series of ACL injured knees with a special focus on ramp lesions of the medial meniscus and posterior root lesions of the lateral meniscus. The hypothesis was that a significant number of ACL injured patients would display these types of lesions. Data from 358 patients undergoing an ACL reconstruction (227 males /131 females, age: 28±10) were extracted from a center-based registry. The type of ACL tear (partial versus complete) as well as the presence of associated meniscus lesions were documented. Meniscus lesions were classified into the following categories: medial ramp lesions, lateral root lesions, medial ramp and lateral root lesion, other medial meniscus injuries, other lateral meniscus injuries, other bimeniscal injuries. Chi-square tests were used to determine whether the percentage of meniscal lesions differed between types of ACL tear, gender and age (below 21, 21–35, above 35). Significance was set at p < 0.05. Isolated ACL tears were present in 107 (30%) of the operated knees (31 partial; 327 complete). Complete ACL lesions were more likely to present an associated meniscus injury (321 out of 327, 71%) than partial tears (13 out of 31, 42%). The incidence of meniscus injuries which are associated with ACL tears is very high (70%). Previously undiagnosed or neglected meniscus injuries like medial ramp or lateral root tears could be identified in 35% of patients. As such, the hypothesis was confirmed that an important amount of ACL injured knees display this specific intraarticular soft tissue damage. A systematic evaluation of these lesions under arthroscopy should thus be performed and specific repair needs to be evaluated

Medial meniscus tear has been proposed as a potential etiology of spontaneous osteonecrosis of the knee (SONK). Disruption of collagen fibers within the meniscus causes meniscal extrusion, which results in alteration in load distribution in the knee. A recent study has demonstrated high incidence of medial meniscus extrusion in the knee with SONK. Our purpose was to determine whether the extent of medial meniscus extrusion correlates with the severity of SONK in the medial femoral condyle. Anteroposterior and lateral knee radiographs were taken with the patients standing. Limb alignment was expressed as the femorotibial angle (FTA) obtained from the anteroposterior radiograph. The stage of progression of SONK was determined according to the radiological classification system described by Koshino. After measurement of anteroposterior, mediolateral, and superoinferior dimensions of the hypointense T1 signal intensity lesion of MRI, its ellipsoid volume was calculated with the three dimensions. Meniscal pathology (degeneration, tear, and extrusion) were also evaluated by MRI. Of the 18 knees with SONK, we found 5 knees at the radiological stage 2 lesions, 9 knees at the stage 3, and 4 knees at the stage 4. Whereas the ellipsoid volume of SONK lesion significantly increased with the stage progression, the volume was significantly greater at stage 4 than stage 2 or 3. All the 18 knees with SONK in the present study showed substantial extrusion (> 3mm) and degeneration of the medial meniscus. While medial meniscal extrusion increased with the stage progression, medial meniscus was significantly extruded at stage 3 or 4 compared with stage 2. A significant increase in FTA was found with the stage progression. FTA was significantly greater at stage 4 than stage 2 or 3. Multiple linear regression analysis revealed that medial meniscus extrusion and FTA were useful predictors of the volume of SONK lesion. This study has clearly shown a significant correlation between the extent of medial meniscus extrusion and the stage and volume of SONK lesion. Degeneration and tears of the medial meniscus in combination with extrusion may result in loss of hoop stress distribution in the medial compartment, which could increase the load in the medial femoral condyle. In addition to meniscal pathology, knee alignment can influence load distribution in the medial compartment biomechanically. Multiple linear regression analysis indicates that an increase in FTA concomitant with a greater extrusion of medial meniscus could result in greater lesion and advanced radiological stage of SONK. Taken together, alteration in compressive force transmission through the medial compartment by meniscus extrusion and varus alignment could develop subchondral insufficiency fractures in the medial femoral condyle, which is considered to be one of the main contributing factors to SONK development. There was high association of medial meniscus extrusion and FTA with the radiological stage and volume of SONK lesion. Increased loading in the medial femoral condyle with greater extrusion of medial meniscus and varus alignment may contribute to expansion and secondary osteoarthritic changes of SONK lesion

Knee arthroscopy is typically approached from the anterior, posteromedial and posterolateral portals. Access to the posterior compartments through these portals can cause iatrogenic cartilage damage and create difficulties in viewing the structures of the posterior compartments. The purpose of this study was to assess the feasibility of needle arthroscopy using direct posterior portals as both working and visualising portals. For workability, the needle scope was inserted advanced from anterior between the cruciate ligament bundle and the lateral wall of the medial femoral condyle until the posterior compartments were visualised. For visualisation, direct postero-lateral and -medial portals were established. The technique was performed in 9 knees by two experienced researchers. Workability and instrumentation of the posteromedial compartment and meniscus was achieved in 56%. The posterior horns could not be visualised in four specimens as the straight lens could not provide a more medial field of view. Visualisation from the direct medial posterior portal allowed a clear view of the medial meniscus, femoral condyle and posterior cruciate ligament in all specimens. Workability and instrumentation of the posterolateral compartment was not possible with the needle scope. Direct posterior approaches for the posteromedial compartment access are challenging with the current needle scope options and could only be achieved in over 50%. The postero-lateral compartment was not accessible. An angled lens or a flexible Needle scope would be better suited for developing this technique further

Abstract. Aims. We studied the outcomes following arthroscopic primary repair of bucket handle meniscus tears to determine the incidence of re-tears and the functional outcomes of these patients. Methodology. Prospective cohort study. Over a 4-year period (2016 to 2020), 35 adult patients presented with a bucket handle tear of the meniscus. Arthroscopic meniscal repair was performed using either the all inside technique or a combination of all-inside and inside-out techniques. 15 patients also underwent simultaneous arthroscopic anterior cruciate ligament reconstruction. Functional knee scores were assessed using IKDC and Lysholm scores. Results. Mean patient age at surgery was 27 years (range, 17 to 53years). Medial meniscus was torn in 20 and lateral in 15 cases. Zone of tear was white on white in 19, red on white in 9 and red on red in 7 cases. Average delay from injury to surgery was 4 months. At a mean follow-up of 4.5 years, the meniscus repair failed in 3 patients (8.5 %). Outcome following re-tear was meniscus excision. Average IKDC scores in patients with intact repair were 74.04 against 56.67 in patients with a failed repair (p< 0.0001). Similarly, Lyshlom scores were 88.96 and 67.333, respectively (p<0.0001). Conclusion. The survivorship of primary repair of bucket handle meniscus tears in our series was 91.5% at medium term follow-up. Functional outcomes were significantly poor in patients with a failed repair compared to those with an intact repair

Aims. We studied the outcomes following arthroscopic primary repair of bucket handle meniscus tears to determine the incidence of re-tears and the functional outcomes of these patients. Methodology. Prospective cohort study. Over a 4-year period (2016 to 2020), 35 adult patients presented with a bucket handle tear of the meniscus. Arthroscopic meniscal repair was performed using either the all inside technique or a combination of all-inside and inside-out techniques. 15 patients also underwent simultaneous arthroscopic anterior cruciate ligament reconstruction. Functional knee scores were assessed using IKDC and Lysholm scores. Results. Mean patient age at surgery was 27 years (range, 17 to 53years). Medial meniscus was torn in 20 and lateral in 15 cases. Zone of tear was white on white in 19, red on white in 9 and red on red in 7 cases. Average delay from injury to surgery was 4 months. At a mean follow-up of 4.5 years, the meniscus repair failed in 3 patients (8.5 %). Outcome following re-tear was meniscus excision. Average IKDC scores in patients with intact repair were 74.04 against 56.67 in patients with a failed repair (p< 0.0001). Similarly, Lyshlom scores were 88.96 and 67.333, respectively (p<0.0001). Conclusion. The survivorship of primary repair of bucket handle meniscus tears in our series was 91.5% at medium term follow-up. Functional outcomes were significantly poor in patients with a failed repair compared to those with an intact repair

Chondrocytic activity is downregulated by compromised autophagy and mitochondrial dysfunction to accelerate the development of osteoarthritis (OA). Irisin is a cleaved form of fibronectin type III domain containing 5 (FNDC5) and known to regulate bone turnover and muscle homeostasis. However, little is known about the role of irisin in chondrocytes and the development of OA. This talk will shed light on FNDC5 expression by human articular chondrocytes and compare normal and osteoarthritic cells with respect to autophagosome marker LC3-II and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG). In chondrocytes in vitro, irisin improves IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production. Irisin further suppressed Sirt3 and UCP- 1 to improve mitochondrial membrane potential, ATP production, and catalase. This attenuated IL-1β-mediated production of reactive oxygen species, mitochondrial fusion, mitophagy, and autophagosome formation. In a surgical murine model of destabilization of the medial meniscus (DMM) intra-articular administration of irisin alleviates symptoms like cartilage erosion and synovitis. Furthermore, gait profiles of the treated limbs improved. In chondrocytes, irisin treatment upregulates autophagy, 8-OHdG and apoptosis in cartilage of DMM limbs. Loss of FNDC5 in chondrocytes correlates with human knee OA and irisin repressed inflammation-mediated oxidative stress and deficient extracellular matrix synthesis through retaining mitochondrial biogenesis and autophagy. The talk sheds new light on the chondroprotective actions of this myokine and highlights the remedial effects of irisin during progression of OA

Abstract. Introduction. The medial meniscus is crescent shaped and it is wider posteriorly than anteriorly. It covers up to 60 % of the articular surface of medial tibial condyle and helps with the loading distribution in the medial compartment. Meniscal lesions occur in association with ACL tears in 60 % of the time. The posterior aspect of the menisco-capsular junction is known as the meniscal rampzone. If not addressed during surgery, it could lead to unfavourable results. Objective. Incidence of ramp lesion following ACL injuries. Methods. Observational study of 100 patients at EL Hadara Main University Hospital who underwent anterior cruciate ligament reconstruction. MRI and arthroscopic diagnosis was done to detect Ramp lesions associated with ACL ruptures in November 2017 till November 2019. Results. Incidence was 9%. Duration of injury and increased medial meniscal slope were associated with increased incidence of ramp lesion. MRI signs were present in 79% of cases without Ramp lesion, 100% in Cases with ramp lesion. Mode of Injury and presence of locking or giving way symptoms were not associated with increased incidence. Conclusion. The ramp lesion at the posterior aspect of the meniscus is difficult to visualize from standard anterior portals and is, therefore, frequently missed and can be underestimated. Also, there are no specific MRI signs of this lesion. The overall incidence of ramp lesions in 100 cases that had undergone ACL reconstruction in our study was 9 %. It was found also that the longer the duration from injury, the more likely ramp lesion would occur. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Introduction. Augmentation of meniscus repairs with fibrin clot may enhance the healing capacity. Pulling the clot into the tear with a suture ensures that it stays in position. This paper aims to assess the outcome of this technique. Methods. 52 patients over 4 years undergoing suture repair of a meniscus tear with blood clot augmentation were collected from a prospective database. Follow up included outcome scores and a questionnaire. Failure was defined as pain or further surgery secondary to meniscal pathology. Results. There were 32 males and 20 females, mean age of 35 (14–70). The medial meniscus was repaired in 32 knees and the lateral in 20. Complete radial tears were the most common type. Only 2% of tears were in the red-red zone. Follow-up ranged from 12 months to 7 years. Only 1 patient is known to have come to subsequent arthroscopy. Lysholm scores improved from 53.97 (SD 18.14) to 92.08 (SD 8.97), Oxford Knee Scores from 29.84 (SD 9.65) to 45.79 (SD 2.66), KOOS pain scores from 61.49 (SD 22.76) to 93.54 (SD 8.06) and Tegner scores from 4.56 (SD 3.35) to 6.05 (SD 2.41). Conclusions. Pulling a fibrin blood clot into a meniscus tear with a suture ensures that the clot remains in place while the meniscus is repaired. Patients have shown excellent outcomes with 98% survivorship at 45 months. This is a reliable technique for augmenting meniscus repairs especially for tears which otherwise may not have been repaired

Autologous micro-fragmented adipose tissue (MFAT) for the treatment of symptomatic knee osteoarthritis (OA) is gaining interest although there is still a lack of supportive data on safety and clinical efficacy. This study primarily aimed to identify patient- and pathology-related parameters to tighten patient selection criteria for future clinical MFAT application. Secondly, the overall (1) therapeutic response rate (TRR), (2) short-term clinical effect, (3) effect durability and (4) therapeutic safety was investigated at a minimal follow-up of 1 year. Sixty-four subjects (91 knees) with symptomatic knee OA (mild-severe on MRI) were enrolled in a prospective single-centre case series. Ethical approval was obtained from the local and academic ethical committee (#B300201733775). After liposuction, the adipose tissue was mechanically processed in a Lipogem® device which eventually produced 6–9cc MFAT. Subjects were clinically assessed by means of the KOOS, NRS, UCLA and EQ-5D at baseline and 1, 3, 6 and 12 months after injection. Adverse events were meticulously recorded. The TRR was defined according to the OMERACT-OARSI criteria. A baseline MRI was scored following the MOAKS system. Paired sample t-tests, independent t-test and Fischer's exact test were applied on appropriate variables. Multiple regression models were fit separately for patient-and pathology-specific factors. Significance level was set at α=0.05. The overall TRR was 66% at 3 months and 50% at 12 months after injection. Subgroup analysis revealed that specifically patients with no-mild bone marrow lesions (BML) had a TRR of 88% at 3 months and 75% at 12 months after MFAT injection. Therapy responders at these timepoints improved with 29.3±14.1 points and 30.8±15.3 points on KOOS pain, while non-responders deteriorated mildly. All clinical scores were significantly higher at follow-up compared to baseline (p<0.05). BMI (factor 0.17, p=0.002) and age (factor −0.48, p=0.048) were prognosticators for the TRR% at 1 month and for absolute KOOS pain improvement at 6 months, respectively. Posterior horn lesions (PHL) in the medial meniscus (p<0.001) and bone marrow lesions (p=0.003) were negative prognosticators for the TRR at respectively 6 and 12 months post-injection. An inflammatory reaction (pain, swelling or stiffness) to MFAT was reported in 79% knees and resolved spontaneously within 16.6±13.5 days after administration. The study showed a durable and satisfying TRR (up to 75% at 1 year in selected patients without BML) and clinical improvement after a single intra-articular injection with autologous MFAT. The availability of an index knee MRI is mandatory to select MFAT patients, preferably with no or mild BML and without PHL of the medial meniscus. High BMI and younger age are associated with better early outcomes. In comparison to other injection therapies such as cortisone, hyaluronic acid and PRP, MFAT appears very attractive with an effect durability of at least 1 year

Abstract. Introduction. Meniscal repair is an accepted surgical option for meniscal tears. However, there remains trepidation with regard to offering such surgery to older patients. We aim to evaluate the outcomes in these such patients. Methodology. A single surgeons log was used to identify patients who underwent meniscal repair and were over the age of 40. Patients having concurrent anterior cruciate ligament reconstructions were excluded. Demographic data, surgical data and outcomes (pain visual analogue score (VAS); single assessment numerical evaluation (SANE) and knee injury and osteoarthritis outcome joint replacement (KOOS Jr) score) were collected prospectively. Final outcomes were collected between 6–12 months following surgery. Results. 24 meniscal tears in 22 knees (22 patients) were identified. Mean age was 52.2 (range; 40.6-70.3). Morphology of the tears were medial meniscus posterior root tear 10 (42%); medial meniscus posterior horn tear 9 (38%); lateral meniscus posterior horn tear 2 (8.3%); lateral meniscus posterior root tear 1 (4.2%); lateral meniscus body tear 1 (4.2%) and lateral meniscus anterior horn tear 1 (4.2%). Response rate was 86%. Statistically significant improvements in pain VAS (p=0.0001); SANE (p=0.0001) and KOOS Jr Score (p=0.0005) were found. 68% and 74% of patients had surpassed the MCID in their KOOS symptoms and KOOS quality of life subscales, respectively. Conclusion. Meniscal repair in patients over 40 years of age is an acceptable treatment with significant improvements in patients reported outcome measures, SANE and pain VAS

A comprehensive understanding of the self-repair abilities of menisci and their overall function in the knee joint requires three-dimensional information. However, previous investigations of the meniscal blood supply have been limited to two-dimensional imaging methods, which fail to accurately capture tissue complexity. In this study, micro-CT was used to analyse the 3D microvascular structure of the meniscus, providing a detailed visualization and precise quantification of the vascular network. A contrast agent (μAngiofil®) was injected directly into the femoral artery of cadaver legs to provide the proper contrast enhancement. First, the entire knee joint was analysed with micro-CT, then to increase the applicable resolution the lateral and medial menisci were excised and investigated with a maximum resolution of up to 4 μm. The resulting micro-CT datasets were analysed both qualitatively and quantitatively. Key parameters of the vascular network, such as vascular volume fraction, vessel radius, vessel length density, and tortuosity, were separately determined for the lateral and medial meniscus, and their four circumferential zones defined by Cooper. In accordance with previous literature, the quantitative micro-CT data confirm a decrease in vascular volume fraction along the meniscal zones. The highest concentration of blood vessels was measured in the meniscocapsular region 0, which is characterized by vascular segments with a significantly larger average radius. Furthermore, the highest vessel length density observed in zone 0 suggests a more rapid delivery of oxygen and nutrients compared to other regions. Vascular tortuosity was detected in all circumferential regions, indicating the occurrence of vascular remodelling in all tissue areas. In conclusion, micro-CT is a non-invasive imaging technique that allows for the visualization of the internal structure of an object in three dimensions. These advanced 3D vascular analyses have the potential to establish new surgical approaches that rely on the healing potential of specific areas of the meniscus. Acknowledgements: The authors acknowledge R. Hlushchuk, S. Halm, and O. Khoma from the University of Bern for their help with contrast agent perfusions

Osteoarthritis (OA) affects the whole joint and leads to chronic pain. The sympathetic nervous system (SNS) seems to be involved in OA pathogenesis, as indicated by in vitro studies as well as by our latest work demonstrating that sympathectomy in mice results in increased subchondral bone volume in the OA knee joint. We assume that chronic stress may lead to opposite effects, such as an increased bone loss in OA due to an elevated sympathetic tone. Therefore, we analyzed experimental OA progression in mice exposed to chronic stress. OA was induced in male C57BL/6J mice by surgical destabilization of the medial meniscus (DMM) and Sham as well as non-operated mice served as controls. Half of these groups were exposed to chronic unpredictable mild stress (CUMS). After 12 weeks, chronic stress efficiency was assessed using behavioral tests. In addition to measuring body weight and length, changes in subchondral bone were analyzed by μCT. Dynamic Weight Bearing system was used to monitor OA-related pain. Histological scoring will be conducted to investigate the severity cartilage degeneration and synovial inflammation. CUMS resulted in increased anxiety and significant decrease in body weight gain in all CUMS groups compared to non-CUMS groups. CUMS also increased serum corticosterone in healthy mice, with even higher levels in CUMS mice after DMM surgery. CUMS had no significant effect on subchondral bone, but subarticular bone mineral density and trabecular thickness were increased. Moreover, CUMS resulted in significant potentiation of DMM-associated pain. Our results suggest that the autonomic imbalance with increased sympathetic nervous activity induced by chronic stress exacerbates the severity of OA pain perception. We expect significantly increased cartilage degeneration as well as more severe synovial inflammation in CUMS DMM mice compared to DMM mice

No proven long-term joint-preserving treatment options exist for patients with irreparable meniscal damage. This study aimed to assess gait kinematics and contact pressures of novel fibre-matrix reinforced polyvinyl alcohol-polyethylene glycol (PVA-PEG) hydrogel meniscus implanted ovine stifle joints against intact stifles in a gait simulator. The gait simulator controlled femoral flexion-extension and applied a 980N axial contact force to the distal end of the tibia, whose movement was guided by the joint natural ligaments (Bartolo; ORS 2021;p1657- LB). Five right stifle joints from sheep aged >2 years were implanted with a PVA-PEG total medial meniscus replacement, fixed to the tibia via transosseous tunnels and interference screws. Implanted stifle joint contact pressures and kinematics in the simulator were recorded and compared to the intact group. Contact pressures on the medial and lateral condyles were measured at 55° flexion using Fujifilm Prescale Low Pressure film inserted under the menisci. 3D kinematics were measured across two 30 second captures using the Optotrak Certus motion-tracking system (Northern Digital Inc.). Medial peak pressures were not significantly different between the implanted and intact groups (p>0.4), while lateral peak pressures were significantly higher in the implanted group (p<0.01). Implanted stifle joint kinematics in the simulator did not differ significantly from the intact baseline (p>0.01), except for in distraction-compression (p<0.01). Our findings show that the fibre-matrix reinforced PVA-PEG hydrogel meniscal replacement restored the medial peak contact pressures. Similar to published literature (Fischenich; ABE 2018;46(11):1–12), the lateral peak pressures in the implanted group were higher than the intact. Joint kinematics were similar across groups, with slightly increased internal-external rotation in the implanted group. These findings highlight the effectiveness of the proposed approach and motivate future work on the development of a total meniscal replacement

Validation of a new meniscal root repair technique that will be biomechanically superior to current gold standard procedures and, at the same time, will allow controlled adjustable fixation. Medial and lateral meniscus from 10 porcine knees were collected. An iatrogenic posterior root tear was created and a single transosseous tibial tunnel technique that closely replicates the repair procedure with a 2-mm-wide-knottable braided tape was performed. Randomly, in one group (A) two simple cinch stitch were applied to suture the posterior root of the meniscus and, in the other group (B), a simple stich that holds the meniscus in two points in a crosse match configuration was used. For final fixation, alternating surgeon's knots (A group) and a doubled suture knot that allows an adjustable fixation were used (B group). All repairs were standardized for location and the repair stiches were placed in the body of the meniscus. The new suture configuration (B group) showed a better biomechanical performance in terms of load for both the medial [151,0-560,3] 306,9±173,8N and the lateral posterior root fixation [268,2-463,1] 347,4±74,3N in comparison to the cinch stitch (A group) [219,0-365,2] 268,9±58,7N and [219,0-413,6] 318,0±72N. The maximum stiffness was also higher for the new tested suture configuration (B group) for both the medial meniscus [10,6-34,5] 18,9±9,2N/mm vs [7,1-12,7] 10,9±2,2N/mm and the lateral meniscus [16,0-27,9] 21,6±5,5N/mm vs [7,6-15,6] 12,6±3,5N/mm. The presented new meniscal root repair is biomechanically superior to current gold standard techniques, as the cinch stich made with tape, keeping the simplicity and reproducibility of the procedure and, at the same time, is economically advantageous since a single tape in needed and allows adjustable fixation of the repair over a button

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA. Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CRE. ERT2. ;Piezo1. fl/fl. Piezo2. fl/fl. ) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria. Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology. Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice

Senescent chondrocyte and subchondral osteoclast overburden aggravate inflammatory cytokine and pro-catabolic proteinase overproduction, accelerating extracellular matrix degradation and pain during osteoarthritis (OA). Fibronectin type III domain containing 5 (FNDC5) is found to promote tissue homeostasis and alleviate inflammation. This study aimed to characterize what role Fndc5 may play in chondrocyte aging and OA development. Serum and macroscopically healthy and osteoarthritic cartilage were biopsied from patients with knee OA who received total knee replacement. Murine chondrocytes were transfected with Fndc5 RNAi or cDNA. Mice overexpressing Fndc5 (Fndc5Tg) were operated to have destabilized medial meniscus mediated (DMM) joint injury as an experimental OA model. Cellular senescence was characterized using RT-PCR analysis of p16INK4A, p21CIP1, and p53 expression together with ß-galactosidase activity staining. Articular cartilage damage and synovitis were graded using OARSI scores. Osteophyte formation and mechanical allodynia were quantified using microCT imaging and von Frey filament, respectively. Osteoclast formation was examined using tartrate-resistant acid phosphatase staining. Senescent chondrocyte and subchondral osteoclast overburden together with decreased serum FNDC5 levels were present in human osteoarthritic cartilage. Fndc5 knockdown upregulated senescence program together with increased IL-6, MMP9 and Adamts5 expression, whereas Alcian blue-stained glycosaminoglycan production were inhibited. Forced Fndc5 expression repressed senescence, apoptosis and IL-6 expression, reversing proliferation and extracellular matrix production in inflamed chondrocytes. Fndc5Tg mice showed few OA signs, including articular cartilage erosion, synovitis, osteophyte formation, subchondral plate sclerosis and mechanical allodynia together with decreased IL-6 production and few senescent chondrocytes and subchondral osteoclast formation during DMM-induced joint injury. Mechanistically, Fndc5 reversed histone H3K27me3-mediated IL-6 transcription repression to reduce reactive oxygen species production. Fndc5 loss correlated with OA development. It was indispensable in chondrocyte growth and anabolism. This study sheds light onto the anti-ageing and anti-inflammatory actions of Fndc5 to chondrocytes; and highlights the chondroprotective function of Fndc5 to compromise OA

TGF-β/Smad2 signaling is considered to be one of the important pathways involved in osteoarthritis (OA) and protein phosphatase magnesium-dependent 1A (PPM1A) functions as an exclusive phosphatase of Smad2 and regulates TGF-β signaling, here, we investigated the functional role of PPM1A in OA pathogenesis. PPM1A expressions in both human OA cartilage and experimental OA mice chondrocytes were analyzed immunohistochemically. Besides, the mRNA and protein expression of PPM1A induced by IL-1β treatment were also detected by q-PCR and immunofluorescence in vitro. OA was induced in PPM1A knockout (KO) mice by destabilization of the medial meniscus (DMM), and histopathological examination was performed. OA was also induced in wild-type (WT) mice, which were then treated with an intra-articular injection of a selective PPM1A inhibitor for 8 weeks. PPM1A protein expressions were increased in both human OA cartilage and experimental OA mice chondrocytes. We also found that treatment with IL-1β in mouse primary chondrocytes significantly increased both mRNA and protein expression of PPM1A in vitro. Importantly, our data showed that PPM1A deletion could substantially protect against surgically induced OA. Concretely, the average OARSI score and quantification of BV/TV of subchondral bone in KO mice were significantly lower than that in WT mice 8 weeks after DMM surgery. Besides, TUNEL staining revealed a significant decrease in apoptotic chondrocytes in PPM1A-KO mice with DMM operation. With OA induction, the rates of chondrocytes positive for Mmp-13 and Adamts-5 in KO mice were also significantly lower than those in WT mice. Moreover, compared with WT mice, the phosphorylation of Smad2 in chondrocytes was increased in KO mice underwent DMM surgery. However, articular-injection with SD-208, a selective inhibitor of TGF-β/Smad2 signaling could significantly abolish the chondroprotective phenotypes in PPM1A-KO mice. Additionally, both cartilage degeneration and subchondral bone subchondral bone sclerosis in DMM model were blunted following intra-articular injection with BC-21, a small-molecule inhibitor for PPM1A. Our study demonstrated that PPM1A inhibition attenuates OA by regulating TGF-β/Smad2 signaling. Furthermore, PPM1A is a potential target for OA treatment and BC-21 may be employed as alternative therapeutic agents for the management of OA

Abstract. Introduction. Elite athletes sustaining a graft re-rupture after ACL reconstruction (ACL-R) undergo revision reconstruction to enable their return to elite sport. The aim of this study was to determine the rate of return to play (RTP) and competition levels at 2 and 5 years post revision ACL-R. Methodology. A consecutive series of revision ACL-R in elite athletes undertaken by the senior author between 2009 and 2019 was retrospectively reviewed. Outcome measures were RTP rates and competition level. Results. Forty-nine athletes underwent revision ACL-R and were included. 87.8% returned to elite sport of which 75.5% were at the same level. At 2 years post-surgery, 79.6% were still playing, 51% at the same level; and at 5 years 44.4% were still playing, 20% at the same level. Athletes with > 50% thickness chondral lesions were less likely to RTP (66.7% vs 94.6%, p = 0.026) and maintain the same competition level (50% vs 83.8%, p = 0.047). Those with medial meniscus pathology were less likely to RTP at the pre-injury level (64.5% vs 94.4%, p = 0.036). Median career length after revision ACL-R was 73 months (95% CI, 43.4 to 102.6), 23 months at the same level (95% CI, 13.6 to 32.4). The probability of still playing at 5 years post-surgery was 55.9% with 22.5% chance of maintaining pre-injury competition level. Conclusion. RTP rates and competition level of elite athletes decreased over time after revision ACL-R. Chondral pathology of > 50% thickness were associated with lower RTP rates and competition levels

Abstract. Objectives. A promising therapy for early osteoarthritis (OA) is the transplantation of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). The synovial fluid (SF) from a pre-clinical ovine model treated with hUC-MSCs has been profiled using proteomics and bioinformatics to elucidate potential mechanisms of therapeutic effect. Methods. Four weeks after a medial meniscus transection surgery, sheep were injected with 10. 7. hUC-MSCs in Phosphate Buffered Saline (PBS) or PBS only (n=7) and sacrificed at 12 weeks. SF was normalised for protein abundance (ProteoMiner. TM. ) and analysed using label-free quantitation proteomics. Bioinformatics analyses (Ingenuity Pathway Analysis (IPA) and STRING) were used to assess differentially regulated functions from the proteomic data. Human orthologues were identified for the ovine proteins using UniProt and DAVID resources and proteins that were ≥±1.3 fold differentially abundant between treatment groups, were included in the bioinformatics analyses. Results. hUC-MSC treated animals demonstrated significantly less joint space narrowing. Nineteen SF proteins were differentially abundant in treated cf. control sheep (FC±2.0; p<0.05). Biglycan (a small leucine-rich proteoglycan of the cartilage extracellular matrix) abundance was increased by 2.1 fold in treated compared to untreated sheep (p=0.024). IPA indicated that lipid synthesis (z-score=1.772; p=0.00267) and immune cell migration pathways (cell movement of mononuclear leukocytes: z-score=1.761; p=0.00259), amongst others, were likely to be activated in the treated sheep. Conversely, tissue damage (z-score=−2; p=0.00019), senescence (z-score=−1.981; p=0.00007) and necrosis (z-score=−1.728; p=0.00829) associated pathways as well as inflammation (z-score=−1.718; p=0.00057) and vascular permeability (z-score=−1.698; p=0.00002) were likely to be inhibited in treated cf. untreated sheep. Conclusions. hUC-MSC treatment prevented/delayed OA progression, demonstrated via a reduction in joint space narrowing. SF proteome bioinformatics revealed potential mechanisms of therapeutic action related to immunomodulation and the inhibition of multiple cell death, and tissue damage associated pathways. Further, a potential predicted upregulation in lipid synthesis in treated sheep represents a novel mechanism warranting further investigation. Additional work is required to validate these discovery phase proteomic findings in studies which specifically target and manipulate the proposed mechanisms highlighted. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Meniscal root tears can result from traumatic injury to the knee or gradual degeneration. When the root is injured, the meniscus becomes de-functioned, resulting in abnormal distribution of hoop stresses, extrusion of the meniscus, and altered knee kinematics. If left untreated, this can cause articular cartilage damage and rapid progression of osteoarthritis. Multiple repair strategies have been described; however, no best fixation practice has been established. To our knowledge, no study has compared suture button, interference screw, and HEALICOIL KNOTLESS fixation techniques for meniscal root repairs. The goal of this study is to understand the biomechanical properties of these fixation techniques and distinguish any advantages of certain techniques over others. Knowledge of fixation robustness will aid in surgical decision making, potentially reducing failure rates, and improving clinical outcomes. 19 fresh porcine tibias with intact medial menisci were randomly assigned to four groups: 1) native posterior medial meniscus root (PMMR) (n = 7), 2) suture button (n = 4), 3) interference screw (n = 4), or 4) HEALICOIL KNOTLESS (n = 4). In 12 specimens, the PMMR was severed and then refixed by the specified group technique. The remaining seven specimens were left intact. All specimens underwent cyclic loading followed by load-to-failure testing. Elongation rate; displacement after 100, 500, and 1000 cycles; stiffness; and maximum load were recorded. Repaired specimens had greater elongation rates and displacements after 100, 500, and 1000 cycles than native PMMR specimens (p 0.05). The native PMMR showed greater maximum load than all repair techniques (p 0.05). In interference screw and HEALICOIL KNOTLESS specimens, failure occurred as the suture was displaced from the fixation and tension was gradually lost. In suture button specimens, the suture was either displaced or completely separated from the button. In some cases, tear formation and partial failure also occurred at the meniscus luggage tag knot. Native PMMR specimens failed through meniscus or meniscus root tearing. All fixation techniques showed similar biomechanical properties and performed inferiorly to the native PMMR. Evidence against significant differences between fixation techniques suggests that the HEALICOIL KNOTLESS technique may present an additional option for fixation in meniscal root repairs. While preliminary in vitro evidence suggests similarities between fixation techniques, further research is required to determine if clinical outcomes differ

Abstract. Cranial cruciate ligament (CrCL) disease/rupture causes pain and osteoarthritis (OA) in dogs. α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 and kainate (KA)-1 glutamate receptors (GluR) and the excitatory amino acid transporter-1 (EAAT-1) and EAAT-3 are expressed in joint tissues from OA patients and rodent arthritis models and represent potential therapeutic targets. Objectives. To evaluate glutamate signalling in canine diseased and normal CrCL and meniscus by immunohistochemistry (IHC). Methods. Surgical waste (CrCL, n=5 and medial meniscus, n=3) were obtained from canines with CrCL disease (RCVS ethics approval:2017/14/Alves) and normal analogous tissues (n=2). IHC optimization was performed for rabbit polyclonal (AMPA-2:ab52176, KA-1:ab67402, EAAT-1:ab416) and monoclonal (EAAT-3:ab124802) antibodies from Abcam. IHC was optimised over antibody dilutions from 1:100 to 1:5000 alongside equivalent IgG isotype controls (ab37415 and ab172730) and negative controls (TBS/Tween buffer without primary antibodies). IHC staining was compared in diseased and normal tissues and disclosed with 3,3’-Diaminobenzidine (DAB). Results. Specific immunostaining was observed for all primary antibodies, at concentrations between 2.0×10. −4. mg/mL to 1.0×10. −2. mg/mL, depending on the tissue and primary antibody. All GluR and transporters were expressed in the cellular membrane, in the normal and diseased CrCL and meniscus. Healthy CrCL showed a well-organized microstructure, with normal positively labelled ligamentocytes, whereas diseased CrCL microstructure was disrupted, with many positively stained fibroblastic cells in the epiligamentous region and evident neovascularization, indicative of ongoing repair. The normal and diseased meniscal tissues showed similar chondrocytes-like cells labelling and microstructure. Negative controls demonstrated no labelling. Conclusions. GluR and transporters expression is altered in canine diseased CrCLs, implicating glutamate signalling in this pathology. Since AMPA/KA GluR antagonists alleviate joint degeneration in post-traumatic OA in rodent models, they may be useful for the treatment of CrCL disease in dogs, as well as translated to other veterinary and human orthopaedic diseases