Objectives. Articular cartilage damage is a primary outcome of pre-clinical and clinical studies evaluating meniscal and cartilage repair or replacement techniques. Recent studies have quantitatively characterized India Ink stained cartilage damage through light reflectance and the application of local or global thresholds. We develop a method for the quantitative characterisation of inked cartilage damage with improved generalisation capability, and compare its performance to the threshold-based baseline approach against gold standard labels. Methods. The Trainable WEKA Segmentation (TWS) tool (Arganda-Carreras et al., 2017) available in Fiji (Rueden et al., 2017) was used to train two separate Random Forest classifiers to automatically segment cartilage damage on ink stained cadaveric ovine stifle joints. Gold standard labels were manually annotated for the training, validation and test datasets for each of the femoral and tibial classifiers. Each dataset included a sample of medial and lateral femoral condyles and tibial plateaus from various stifle joints, selected to ensure no overlap across datasets according to ovine identifier. Training was performed on the training data with the TWS tool using edge, texture and noise reduction filters selected for their suitability and performance. The two trained classifiers were then applied to the validation data to output damage probability maps, on which a threshold value was calibrated. Model predictions on the unseen test set were evaluated against the gold standard labels using the Dice Similarity Coefficient (DSC) – an overlap-based metric, and compared with results for the baseline global threshold approach applied in Fiji as shown in Figures 1 and 2. Results. Test set results for the global threshold approach against gold standard labels were 45.0% DSC for the femoral condyle and 32.0% DSC for the tibial plateau. Results for the developed TWS classifiers on the same unseen test data were 79.0% and 72.7% DSC, showing absolute gains of 34.0% and 40.7% DSC over the global threshold baseline for the femoral and tibial classifiers. The trained TWS classifiers were then applied to an external set of unlabelled images of ink stained femoral condyles and tibial plateaus. Model results on sample images shown in Figure 3 further highlight the generalisation capability of the developed models. The most prominent classification features were Hessian filters (32.9%), Entropy (19.4%), Gaussian blur (10.1%), Gabor filters (6.3%) and Sobel filters (6.0%), with all other features contributing less than 6%. Conclusions. Our findings show that the developed segmentation method more accurately quantifies cartilage damage and provides improved generalisation capability over a range of input variations such as inconsistent orientation and lighting conditions. The developed model enables the use of articular cartilage damage as a reliable and quantitative outcome measure in studies involving large datasets, with reduced requirements for complex pre-processing and specialised equipment. For any figures or tables, please contact the authors directly

Aims. Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD. Methods. The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between COMP-overexpression groups and control groups were examined after cell transfection. Results. The mRNA and protein expression levels of COMP were significantly lower in KBD chondrocytes than control chondrocytes. After the T-2 toxin intervention, the COMP mRNA expression of C28/I2 chondrocyte reduced and the protein level of COMP in three intervention groups was significantly lower than in the control group. MTT assay showed that the survival rate of COMP overexpression KBD chondrocytes were notably higher than in the blank control group. The mRNA expression levels of Survivin, SOX9, Caspase-3, and type II collagen were also significantly different among COMP overexpression, negative control, and blank control groups. Conclusion. Our study results confirmed the functional relevance of COMP with KBD. COMP may play an important role in the excessive chondrocytes apoptosis of KBD patients. Cite this article: Bone Joint Res 2020;9(9):578–586

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

INTRODUCTION

Osteoarthritis (OA) can be artificially simulated ex vivo on healthy articular cartilage (AC) samples by use of proteolytic enzymes. In this article we will present preliminary analyses of the physical degradation of AC when subjected to alternating mechanical stresses. Since AC damage due to OA is believed to be mechanically induced, the first step towards the realisation of an improved understanding of degenerative behaviour of AC under physiological loading conditions is to perform ex vivo tests which mimic such conditions at best.

Background

The purpose of this study was to report functional outcome scores following arthroscopic acetabular chondral procedures using the U.K. Non-Arthroplasty Hip Registry (NAHR).

Aims. Hip arthroscopy (HA) has become the treatment of choice for femoroacetabular impingement (FAI). However, less favourable outcomes following arthroscopic surgery are expected in patients with severe chondral lesions. The aim of this study was to assess the outcomes of HA in patients with FAI and associated chondral lesions, classified according to the Outerbridge system. Methods. A systematic search was performed on four databases. Studies which involved HA as the primary management of FAI and reported on chondral lesions as classified according to the Outerbridge classification were included. The study was registered on PROSPERO. Demographic data, patient-reported outcome measures (PROMs), complications, and rates of conversion to total hip arthroplasty (THA) were collected. Results. A total of 24 studies were included with a total of 3,198 patients (3,233 hips). Patients had significantly less improvement in PROMs if they had Outerbridge grade III and IV lesions (p = 0.012). Compared with microfracture, autologous matrix-induced chondrogenesis (AMIC) resulted in significantly reduced rates of conversion to THA (p = 0.042) and of revision arthroscopy (p = 0.038). Chondral repair procedures in these patients also did not significantly reduce the rates of conversion to THA (p = 0.931), or of revision arthroscopy (p = 0.218). However, compared with microfracture, AMIC significantly reduced the rates of conversion to THA (p = 0.001) and of revision arthroscopy (p = 0.011) in these patients. Those with Outerbridge grade III and IV lesions also had significantly increased rates of conversion to THA (p = 0.029) and of revision arthroscopy (p = 0.023) if they had associated lesions of the acetabulum and femoral head. Those who underwent labral debridement had a significantly increased rate of conversion to THA compared with those who underwent labral repair (p = 0.015). Conclusion. There is universal improvement in PROMs following HA in patients with FAI and associated chondral lesions. However, those with Outerbridge grade III and IV lesions had significantly less improvement in PROMs and a significantly increased rate of conversion to THA than those with Outerbridge grade I and II. This suggests that the outcome of HA in patients with FAI and severe articular cartilage damage may not be favourable. Cite this article: Bone Joint J 2023;105-B(7):751–759

Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions. PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared. 9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies. This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context

Development of osteoarthritis (OA) correlates with epigenetic alteration in chondrocytes. H3K27me3 demethylase UTX is known to regulate tissue homeostasis, but its role in the homeostasis of articulating joint tissue is poorly understood. Forced UTX expression upregulated H3K27me3 enrichment at the Sox9 promoter region to inhibit key extracellular matrix (ECM) molecules, like e.g. type II collagen, aggrecan, and glycosaminoglycans in articular chondrocytes. Utx loss in vitro altered the H3K27me3-binding epigenomic landscape, which contributes to mitochondrial activity, cellular senescence, and cartilage development. Functional target genes of Utx comprise insulin-like growth factor 2 (Igf2) and polycomb repressive complex 2 (PRC2) core components Eed and Suz12. Specifically, Utx deletion promoted Tfam transcription, mitochondrial respiration, ATP production and Igf2 transcription, but inhibited Eed and Suz12 expression. Igf2 inhibition or forced Eed or Suz12 expression increased H3K27 trimethylation and H3K27me3 enrichment at the Sox9 promoter, compromising Utx loss-induced ECM overproduction. Overexpression of Utx in murine knee joints aggravated OA development, including articular cartilage damage, synovitis, osteophyte formation, and subchondral bone loss. Transgenic mice with a chondrocytespecific Utx knockout develop thicker articular cartilage as compared to wild-type controls and show fewer gonarthrotic symptoms during destabilized medial meniscus- and collagenase-induced joint injury. In summary, UTX represses chondrocytic activity and accelerates cartilage degradation during OA, while Utx loss promotes cartilage integrity through epigenetic stimulation of mitochondrial biogenesis and Igf2 transcription. This highlights a novel noncanonical role of Utx that regulates articular chondrocyte anabolism and OA development

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

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

Aims. To investigate the risk factors for progression of articular cartilage damage after anatomical anterior cruciate ligament (ACL) reconstruction. Patients and Methods. A total of 174 patients who underwent second-look arthroscopic evaluation after anatomical ACL reconstruction were enrolled in this study. The graded condition of the articular cartilage at the time of ACL reconstruction was compared with that at second-look arthroscopy. Age, gender, body mass index (BMI), ACL reconstruction technique, meniscal conditions, and other variables were assessed by regression analysis as risk factors for progression of damage to the articular cartilage. Results. In the medial compartment, multivariable logistic regression analysis indicated that partial medial meniscectomy (odds ratio (OR) 6.82, 95% confidence interval (CI) 2.11 to 22.04, p = 0.001), pivot-shift test grade at the final follow-up (OR 3.53, CI 1.39 to 8.96, p = 0.008), BMI (OR 1.15, CI 1.03 to 1.28, p = 0.015) and medial meniscal repair (OR 3.19, CI 1.24 to 8.21, p = 0.016) were significant risk factors for progression of cartilage damage. In the lateral compartment, partial lateral meniscectomy (OR 10.94, CI 4.14 to 28.92, p < 0.001) and side-to-side differences in anterior knee laxity at follow-up (OR 0.63, p = 0.001) were significant risk factors. Conclusion. Partial meniscectomy was found to be strongly associated with the progression of articular cartilage damage despite r anatomical ACL reconstruction. Cite this article: Bone Joint J 2018;100-B:285–93

Introduction. Articular cartilage injuries have a limited potential to heal and, over time, may lead to osteoarthritis, an inflammatory and degenerative joint disease associated with activity-related pain, swelling, and impaired mobility. Regeneration and restoration of the joint tissue functionality remain unmet challenges. Stem cell-based tissue engineering is a promising paradigm to treat cartilage degeneration. In this context, hydrogels have emerged as promising biomaterials, due to their biocompatibility, ability to mimic the tissue extracellular matrix and excellent permeability. Different stimulation strategies have been investigated to guarantee proper conditions for mesenchymal stem cell differentiation into chondrocytes, including growth factors, cell-cell interactions, and biomaterials. An interesting tool to facilitate chondrogenesis is external ultrasound stimulation. In particular, low-intensity pulsed ultrasound (LIPUS) has been demonstrated to have a role in regulating the differentiation of adipose mesenchymal stromal cells (ASCs). However, chondrogenic differentiation of ASCs has been never associated to a precisely measured ultrasound dose. In this study, we aimed to investigate whether dose-controlled LIPUS is able to influence chondrogenic differentiation of ASCs embedded in a 3D hydrogel. Materials and Methods. Human adipose mesenchymal stromal cells at 2∗10. 6. cells/mL were embedded in a hydrogel ratio 1:2 (VitroGel RGD®) and exposed to LIPUS stimulation (frequency: 1 MHz, intensity: 250 mW/cm. 2. , duty cycle: 20%, pulse repetition frequency: 1 kHz, stimulation time: 5 min) in order to assess its influence on cell differentiation. Hydrogel-loaded ASCs were cultured and differentiated for 2, 7, 10 and 28 days. At each time point cell viability (Live&Dead), metabolic activity (Alamar Blue), cytotoxicity (LDH), gene expression (COL2, aggrecan, SOX9, and COL1), histology and immunohistochemistry (COL2, aggrecan, SOX9, and COL1) were evaluated respect to a non-stimulated control. Results. Histological analysis evidenced a uniform distribution of ASCs both at the periphery and at the center of the hydrogel. Live & Dead test evidenced that the encapsulated ASCs were viable, with no signs of cytotoxicity. We found that LIPUS induced chondrogenesis of ASCs embedded in the hydrogel, as demonstrated by increased expression of COL2, aggrecan and SOX9 genes and proteins, and decreased expression of COL1 respect to the non-stimulated control. Conclusions. These results suggest that the LIPUS treatment could be a valuable tool in cartilage tissue engineering, to push the differentiation of ASCs encapsulated in a 3D hydrogel

Abstract. Objective. Articular cartilage damaged through trauma or disease has a limited ability to repair. Untreated, these focal lesions progress to generalized changes including osteoarthritis. Musculoskeletal disorders including osteoarthritis are the most significant contributor to disability globally. There is increasing interest in the use of mesenchymal stem cells (MSCs) for the treatment of focal chondral lesions. There is some evidence to suggest that the tissue type from which MSCs are harvested play a role in determining their ability to regenerate cartilage in vitro and in vivo. In humans, MSCs derived from synovial tissue may have superior chondrogenic potential. Methods. We carried out a systematic literature review on the effectiveness of synovium-derived MSCs (sMSCs) in cartilage regeneration in in vivo studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Nineteen studies were included in our review; four examined the use of human sMSCs and the remainder were conducted using sMSCs harvested from animals. Results. Despite the variability of animals, cell harvesting techniques, methods of delivery, and outcome measures, all studies reported successful cartilage repair with sMSC transplantation. Conclusion. We conclude that sMSC transplantation holds promise as a treatment option for focal cartilage defects. We believe that defining the cell population being used, establishing standardized methods for MSC delivery, and the use of objective outcome measures should enable future high-quality studies such as randomized controlled clinical trials to provide the evidence needed to manage chondral lesions optimally. 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

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

The purpose of the present study is to determine a correlation between articular cartilage changes and underlying bone contusions in ACL-deficient knees. Analysis of surgical and MRI findings in thirty-seven knees shows that medial femoral condyle and medial tibial plateau bone contusions, present in 30% of ACL injuries, correlate strongly with articular cartilage damage, irrespective of meniscal status. Although lateral compartment bone contusions are more commonly seen following injury, we have not found this to be associated with the status of the overlying cartilage. Degenerative changes in the ACL-deficient knee are multifactorial, but medial compartment bone contusions may be an important contributor that warrants further investigation. Despite successful reconstruction of the anterior cruciate ligament, many patients eventually develop osteoarthritis, suggesting that something in addition to mechanical instability may contribute. The purpose of the present study is to determine a correlation between articular cartilage changes and underlying bone contusions in ACL-deficient knees. Between January 2002 and March 2003, sixty-eight knees consecutively underwent ACL reconstruction at our institution. Presence and location of bone contusions on MRI were noted, and correlated to presence of articular cartilage changes and meniscal pathology witnessed during surgery. Of the sixty-eight knees operated, thirty-one were excluded because of either: pre-existing arthritis, previous surgery, presence of multiple ligament injury, or absence of bone contusions on MRI. In the analysis of the thirty-seven remaining knees, bone contusions were present on the medial tibial plateau and medial femoral condyle in 30%, on the lateral tibial plateau in 84%, and on the lateral femoral condyle in 73%. Articular cartilage damage is most commonly seen on the medial femoral condyle, irrespective of meniscal status. Analysis using Fisher’s Exact test shows that medial femoral condyle (p=0.026) and medial tibial plateau articular cartilage damage (p= 0.011) is strongly correlated with presence of underlying bone contusions. No association was found between lateral compartment articular cartilage status and presence of bone contusions. Although lateral compartment bone contusions are common following ACL injuries, we have not found an association with cartilage damage. Degenerative changes in the ACL-deficient knee are multifactorial, but medial compartment bone contusions may be an important contributor

Aberrant infrapatellar fat metabolism is a notable feature provoking inflammation and fibrosis in the progression of osteoarthritis (OA). Irisin, a secretory subunit of fibronectin type III domain containing 5 (FNDC5) regulate adipose morphogenesis, energy expenditure, skeletal muscle, and bone metabolism. This study aims to characterize the biological roles of Irisin signaling in an infrapatellar fat formation and OA development. Injured articular specimens were harvested from 19 patients with end-stage knee OA and 11 patients with the femoral neck fracture. Knee joints in mice that overexpressed Irisin were subjected to intra-articular injection of collagenase to provoke OA. Expressions of Irisin, adipokines, and MMPs probed with RT-quantitative PCR. Infrapatellar adiposity, articular cartilage damage, and synovial integrity verified with histomorphometry and immunohistochemistry. Infrapatellar adipose and synovial tissues instead of articular cartilage exhibited Irisin immunostaining. Human OA specimens showed 40% decline in Irisin expression than the non-OA group. In vitro, the gain of Irisin function enabled synovial fibroblasts but not chondrocytes to display minor responses to the IL-1β provocation of MMP3 and MMP9 expression. Of note, Irisin signaling reduced adipogenic gene expression and adipocyte formation of mesenchymal progenitor cells. In collagenase-mediated OA knee pathogenesis, forced FNDC5 expression in articular compromised the collagenase-induced infrapatellar adipose hypertrophy, synovial hypercellularity, and membrane hyperplasia. These adipose-regulatory actions warded off the affected knees from cartilage destruction and gait aberrance. Likewise, intra-articular injection of Irisin recombinant protein mitigated the development of infrapatellar adiposity and synovitis slowing down the progression of cartilage erosion and walking profile irregularity. Affected joints and adipocytes responded to the Irisin recombinant protein treatment by reducing the expressions of cartilage-deleterious adipokines IL-6, leptin, and adiponectin through regulating PPAR&gamma, function. Irisin dysfunction is relevant to the existence of end-stage knee OA. Irisin signaling protects from excessive adipogenesis of mesenchymal precursor cells and diminished inflammation and cartilage catabolism actions aggravated by adipocytes and synovial cells. This study sheds emerging new light on the Irisin signaling stabilization of infrapatellar adipose homeostasis and the perspective of the therapeutic potential of Irisin recombinant protein for deescalating knee OA development

We describe 119 meniscal allograft transplantations performed concurrently with articular cartilage repair in 115 patients with severe articular cartilage damage. In all, 53 (46.1%) of the patients were over the age of 50 at the time of surgery. The mean follow-up was for 5.8 years (2 months to 12.3 years), with 25 procedures (20.1%) failing at a mean of 4.6 years (2 months to 10.4 years). Of these, 18 progressed to knee replacement at a mean of 5.1 years (1.3 to 10.4). The Kaplan-Meier estimated mean survival time for the whole series was 9.9 years (. sd. 0.4). Cox’s proportional hazards model was used to assess the effect of covariates on survival, with age at the time of surgery (p = 0.026) and number of previous operations (p = 0.006) found to be significant. The survival of the transplant was not affected by gender, the severity of cartilage damage, axial alignment, the degree of narrowing of the joint space or medial versus lateral allograft transplantation. Patients experienced significant improvements at all periods of follow-up in subjective outcome measures of pain, activity and function (all p-values < 0.05), with the exception of the seven-year Tegner index score (p = 0.076)

Articular cartilage injury has a high prevalence in elite and recreational athletes. Articular cartilage repair remains a challenge due to cost effectiveness and clinical effectiveness issues. There are now several effective technologies and it is possible to return to competitive sports following many of the procedures available. The durability of repair tissue is variable and there remains extensive growth in the Scientific world. Evolving cartilage restoration technologies focus on increasing cartilage quality and quantity, while optimising surgery and rehabilitation. In UK ACI has undergone extensive cost effectiveness analysis and the in-depth review has shown that ACI is cost effective compared to microfracture. ACI is indicated for lesions >2cm sq but NICE has considered that it is not indicated for problems after microfracture. This presentation details the various options available to surgeons and examines the cost effectiveness