Syndesmotic ankle lesions involve disruption of the osseous tibiofibular mortise configuration as well as ligamentous structures stabilizing the ankle joint. Incomplete diagnosis and maltreatment of these injuries is frequent, resulting in chronic pain and progressive instability thus promoting development of ankle osteoarthritis in the long term. Although the pathogenesis is not fully understood, abnormal mechanics has been implicated as a principal determinant of ankle joint degeneration after syndesmotic ankle lesions. Therefore, the focus of this presentation will be on our recent development of a computationally efficient algorithm to calculate the contact pressure distribution in patients with a syndesmotic ankle lesion, enabling us to stratify the risk of OA development in the long term and thereby guiding patient treatment

Stimulation of the mechanosensitive ion channel, Piezo1 promotes bone anabolism and SNPs in the Piezo1 locus are associated with changes in fracture risk. Osteocytes function as critical regulators of bone homeostasis by sensing mechanical signals. The current study used a human, cell-based physiological, 3D in vitro model of bone to determine whether loading of osteocytes in vitro results in upregulation of the Piezo1 pathway. Human Y201 MSCs, embedded in type I collagen gels and differentiated to osteocytes for 7-days, were subjected to pathophysiological load (5000 µstrain, 10Hz, 5 mins; n=6) with unloaded cells as controls (n=4). RNA was extracted 1-hr post load and assessed by RNAseq analysis. To mimic mechanical load and activate Piezo1, cells were differentiated to osteocytes for 13 days and treated ± Yoda1 (5µM, 2- and 24-hs, n=4); vehicle treated cells served as controls (n=4). RNA was subjected to RT-qPCR and data normalised to the housekeeping gene, YWHAZ. Media was analysed for IL6 release by ELISA. Mechanical load upregulated Piezo1 gene expression (16.5-fold, p<0.001) and expression of the transcription factor NFATc1, and matricellular protein CYR61, known regulators of Piezo1 mechanotransduction (3-fold; p= 5.0E-5 and 6.8-fold; p= 6.0E-5, respectively). After 2-hrs, Yoda1 increased the expression of the early mechanical response gene, cFOS (11-fold; p=0.021), mean Piezo1 expression (2.3-fold) and IL-6 expression (103-fold, p<0.001). Yoda1 increased the release of IL6 protein after 24 hours (7.5-fold, p=0.001). This study confirms Piezo1 as an important mechanosensor in osteocytes. Piezo1 activation mediated an increase in IL6, a cytokine that drives inflammation and bone resorption providing a direct link between mechanical activation of Piezo1, bone remodeling and inflammation, which may contribute to mechanically induced joint degeneration in diseases such as osteoarthritis. Mechanistically, we hypothesize this may occur through promoting Ca2+ influx and activation of the NFATc1 signaling pathway

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

Abstract. Objectives. Osteocytes function as critical regulators of bone homeostasis by sensing mechanical signals. Stimulation of the mechanosensitive ion channel, Piezo1 promotes bone anabolism and deletion of Piezo1 in osteoblasts and osteocytes decreases bone mass and bone strength in mice. This study determined whether loading of osteocytes in vitro results in upregulation of the Piezo1 pathway. Methods. Human MSC cells (Y201), embedded in type I collagen gels and differentiated to osteocytes in osteogenic media for 7-days, were subjected to pathophysiological load (5000 µstrain, 10Hz, 5 mins; n=6) with unloaded cells as controls (n=4). RNA was extracted 1-hr post load and Piezo1 activation assessed by RNAseq analysis (NovaSeq S1 flow cell 2 × 100bp PE reads). To mimic mechanical load and activate Piezo1, Y201s were differentiated to osteocytes in 3D gels for 13 days and treated, with Yoda1 (5µM, 2 hours, n=4); vehicle treated cells served as controls (n=4). Extracted RNA was subjected to RT-qPCR and data analysed by Minitab. Results. Low mRNA expression of PIEZO1 in unloaded cells was upregulated 5-fold following 1-hr of mechanical load (p=0.003). In addition, the transcription factor NFATc1, a known regulator of Piezo1 mechanotransduction, was also upregulated by load (2.4-fold; p=0.03). Y201 cells differentiated in gels expressed the osteocyte marker, SOST. Yoda1 upregulated PIEZO1 (1.7-fold; p=0.057), the early mechanical response gene, cFOS (4-fold; p=0.006), COL1A1 (3.9-fold; p=0.052), and IL-6 expression (7.7-fold; p=0.001). Discussion. This study reveals PIEZO1 as an important mechanosenser in osteocytes. Piezo 1 mediated increases in the bone matrix protein, type I collagen, and IL-6, a cytokine that drives inflammation and bone resorption. This provides a direct link between mechanical activation of Piezo 1, bone remodelling and inflammation, which may contribute to mechanically-induced joint degeneration in osteoarthritis. Mechanistically, we hypothesise this may occur through promoting Ca2+ influx and activation of the NFAT1 signalling pathway

Abstract. Objectives. Osteoarthritis (OA) is a painful and debilitating disorder of diarthroidal joints. Progressive degeneration of the cartilage extracellular matrix (ECM) together with abnormal chondrocyte characteristics occur leading to a switch to a fibroblast-like phenotype and production of mechanically-weak cartilage. Early changes to chondrocytes within human cartilage have been observed including chondrocyte swelling. [1]. together with the development of thin cytoplasmic processes which increase in number and length with degeneration. [2]. Changes to chondrocyte phenotype in degenerate cartilage are associated with F-actin redistribution and stress fibres (SF) formation, leading to morphologically-dedifferentiated (fibroblast-like) chondrocytes. [3,4]. It is unclear if these processes are a consequence of ‘passive’ cell swelling into a defective ECM or an ‘active’ event driven by changes in cell metabolism resulting in alterations to cell shape. To address this, we have quantified and compared the distribution and levels of F-actin, a key cytoskeletal protein involved in the formation of cytoplasmic processes, within in situ chondrocytes in non-degenerate and mildly degenerate human cartilage. Methods. Human femoral head cartilage was obtained from 21 patients [15 females, 6 males, average age 69.6yrs, (range 47–90yrs)] following femoral neck fracture, with Ethical Approval and patient's permission. Cartilage explants were removed from areas graded non-degenerate grade 0 (G0) or mildly degenerate grade 1 (G1) and cultured for up to 3wks in Dulbecco's Modified Eagle's Medium (DMEM) +/− 25% human serum (HS). In situ chondrocytes were stained with CMFDA (5-chloromethylfluoresceindiacetate, Cell-Tracker Green®) and phalloidin (F-actin labelling) and imaged by confocal microscopy and analysed quantitatively using ImageJ and Imaris® software. Results. There were significant increases in the total amount (TA) of F-actin and its distribution [intense punctuate (IP) and intense areas (IA)] between the whole chondrocyte populations of G0 and G1 cartilage (P=0.0356; 0.0112; 0.016, respectively). Where the volume of chondrocytes was divided into normal (<1000 µm³) and swollen (≥1000 µm³) cells, F-actin TA increased in swollen cells (P=0.036 within G0 and G1, and P=0.0009 between grades) compared to chondrocytes of normal volume in each grade. Moreover, IP and IA within and between G0 and G1 were higher compared to normal chondrocytes (with P<0.0001 for IP and P<0.001 for IA). In addition, tissue culture experiments demonstrated that 90% of chondrocytes with cytoplasmic processes had strong F-actin intensity (either IP or IA with P<0.0001). Furthermore, 83% of this F-actin was associated with cytoplasmic processes, with >65% situated at the base of the process (P<0.0001). Conclusions. The increases in chondrocyte F-actin levels (TA) and its localisation (IP, IA) appear to be associated with cell swelling and development of cytoplasmic processes, which are both characteristics of early OA cartilage. [1]. This suggests the formation of chondrocyte cytoplasmic processes is an ‘active’ event potentially involving changes to matrix metabolism rather than a ‘passive’ cell swelling into a defective extracellular matrix. 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. OBJECTIVES. Abnormal joint mechanics have been proposed as adversely affecting natural hip joint tribology, whereby increased stress on the articular cartilage from abnormal loading leads to joint degeneration. The aim of this project was to assess the damage caused by different loading conditions on the articular surfaces of the porcine hip joint in an experimental simulator. METHODS. Porcine hip joints were dissected and mounted in a single station hip simulator (SimSol, UK) and tested under loading scenarios (that corresponded to equivalent of different body mass index's’ (BMI) in humans), as follows:“Normal” (n=4), the loading cycle consisted of a simplified gait cycle based on a scaled version of a simplified twin-peak human gait cycle, the peak load was 900N (representative of a healthy BMI). Representative of an “Overweight” BMI (n=3), as the normal cycle with a peak load of 1,130N Representative of an “Obese” BMI (n=1), as the normal cycle with a peak load of 1,340N Tests were conducted at 1Hz for 14,400 cycles in Ringers solution; photogrammetry was used to characterise the appearance of the cartilage and labrum pre, during and post simulation. the appearance and location of damage was recorded. RESULTS. No significant damage was observed for samples tested under normal conditions. Following “overweight” condition testing, tears and detachment of the labrum were observed during testing in two (of three) samples. In addition to damaged observed in “overweight” tested samples the “obese” showed similar damage and also cartilage bruising and wear tracks on the articular surface of the acetabulum. DISCUSSION. The absence of damage in “normal” loading provides evidence that this is an appropriate methodology and loading regime for porcine hips. Increased damage with increasing loads demonstrates the potential to develop further this experimental simulation to assess adverse loading in natural hip joints. 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. OBJECTIVES. Although surgical periacetabular osteotomy (PAO) for hip dysplasia aims to optimise acetabular coverage and restore hip function, it is unclear how surgery affects capsular mechanics and joint stability. The purpose was to examine how the reoriented acetabular coverage affects capsular mechanics and joint stability in dysplastic hips. METHODS. Twelve cadaveric dysplastic hips (n = 12) were denuded to the capsule and mounted onto a robotic tester. The robot positioned each hip in multiple flexion angles (Extension, Neutral 0°, Flexion 30°, Flexion 60°, Flexion 90°) and performed internal-external rotations and abduction-adduction to 5 Nm in each rotational or planar direction. Each hip underwent a PAO, preserving the capsule, and was retested postoperatively in the robot. Paired sample t-tests compared the range of motion before and after PAO surgery (CI = 95%). RESULTS. Pre-operatively, the dysplastic hips demonstrated large ranges of internal-external rotations and abduction-adduction motions throughout all flexion positions. Post-operatively, the PAO slackenend the anterosuperior capsule and tightened the inferior capsule. This increased external rotation in Flexion 60° and Flexion 90° (∆. ER. = +16 and +23%) but provided lateral coverage to decrease internal rotation at Flexion 90° (∆. IR. = –15%). The PAO also reduced abduction throughout, but increased adduction in Neutral 0°, Flexion 30°, and Flexion 60° (∆. ADD. = +34, +30%, +29% respectively). CONCLUSIONS. The PAO provided crucial osseous structural coverage to the femoral head, decreasing hypermobility and adverse loading at extreme hip flexion-extension. However, it also slackened the anterosuperior capsule and increased adduction and external rotation, which may lead to ischiofemoral impingement and adductor irritations. Capsular instability may be secondary to acetabular undercoverage, thus capsular alteration may be warranted for larger corrections or rotational osteotomies. To preserve native hip and delay joint degeneration, it is crucial to preserve capsule and elucidate amount of reorientation needed without causing iatrogenic instability. 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. Objectives. The mechanisms underlying abnormal joint mechanics are poorly understood despite it being a major risk factor for developing osteoarthritis. This study investigated the response of a 3D in vitro bone cell model to mechanical load. Methods. Human MSC cells (Y201) embedded in 3D type I collagen gels were differentiated in osteogenic media for 7-days in deformable, silicone plates. Gels were loaded once (5000 µstrain, 10Hz, 3000 cycles), RNA extracted 1-hr post load and assessed by RT-qPCR and RNAseq analysis (n=5/treatment). Cell shape and phenotype were assessed by immunocytochemistry and phalloidin staining. Data was analysed by Minitab. Results. RTqPCR revealed cells expressed markers of mature osteocytes (E11, sclerostin, DMP-1) and osteoprotegerin (OPG), alkaline phosphatase and type I collagen (COL1A1). Immunolocalisation of sclerostin and DMP-1 protein along with phalloidin staining confirmed a dendritic osteocyte phenotype. Load almost abolished sclerostin gene expression (p=0.05) and reduced E11 (2-fold p=0.03); COL1A1 was unchanged (p=0.349). Using DEseq2 analysis, of the 981 genes differentially regulated more than 2-fold at FDR p<0.05, 159 were downregulated and 821 upregulated by load. These were involved in processes important in bone biology including the inflammatory response (56 genes), ECM organisation (27), ageing (30), response to mechanical load (23), ER stress (34), regulation of ossification (26), bone morphogenesis (14), cartilage development (14), programmed cell death (161), and positive regulation of bone mineralisation (6). Discussion. Y201 cells were successfully differentiated to osteocytes. The osteocytes’ mechanical response revealed regulation of factors that contribute to bone remodelling and inflammation. Since the biological mechanisms underlying mechanically induced joint degeneration are unclear, there is a need for humanised, cell models to delineate molecular pathways activated by mechanical load. Such pathways may reveal the molecular basis for genetic predispositions to osteoarthritis and identify new therapeutic targets. 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. OBJECTIVES. Cam femoroacetabular impingement (FAI – femoral head-neck deformity) and developmental dysplasia of the hip (DDH – insufficient acetabular coverage) constitute a large portion of adverse hip loading and early degeneration. Spinopelvic anatomy may play a role in hip stability thus we examined which anatomical relationships can best predict range of motion (ROM). METHODS. Twenty-four cadaveric hips with cam FAI or DDH (12:12) were CT imaged and measured for multiple femoral (alpha angles, head-neck offset, neck angles, version), acetabular (centre-edge angle, inclination, version), and spinopelvic features (pelvic incidence). The hips were denuded to the capsule and mounted onto a robotic tester. The robot positioned each hip in multiple flexion angles (Extension, Neutral 0°, Flexion 30°, Flexion 60°, Flexion 90°); and performed internal-external rotations to 5 Nm in each position. Independent t-tests compared the anatomical parameters and ROM between FAI and DDH (CI = 95%). Multiple linear regressions determined which anatomical parameters could predict ROM. RESULTS. The FAI group demonstrated restricted ROM in deep hip flexion, with DDH showing higher ROM in Flexion 30° (+20%, p = 0.03), 60° (+31%, p = 0.001), and 90° (+36%, p = 0.001). In Neutral 0° and Flexion 30°, femoral neck and version angles together predicted ROM (R. 2. = 60%, 58% respectively); whereas in Flexion 60°, pelvic incidence and femoral neck angle predicted ROM (R. 2. = 77%). In Flexion 90°, pelvic incidence and radial alpha angle together predicted ROM (R. 2. = 81%), where pelvic incidence alone accounted for 63% of this variance. CONCLUSIONS. Pelvic incidence is essential to predict hip ROM. Although a cam deformity or acetabular undercoverage can elevate risks of labral tears and progressive joint degeneration, they may not be primary indicators of restrictive hip impingement or dysplastic instability. Better delineating additional spinopelvic characteristics can formulate early diagnostic tools and improve opportunities for nonsurgical management. 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

Osteoarthritis (OA), characterised by pain, disability and joint degeneration, is common and has no cure. Prevalence of severe radiographic knee OA is 19% in over 45's and 50% in over 75's in the US and Europe. Abnormal joint loading, or injury, increase risk of OA. We have discovered that glutamatergic signalling is mechanically regulated and glutamate receptors (GluR) drive inflammation, degeneration and pain representing potential drug targets in osteoarthritic joints. Joints from OA and knee injured patients, and rodent models of arthritis, show increased synovial fluid glutamate concentrations and abundant GluR expression. Since AMPA/kainate GluRs regulate IL-6, a critical mediator of arthritic degeneration, we tested protective effects of the AMPA/KA GluR antagonist, NBQX in animal models of arthritis. In rodent antigen induced arthritis, and osteoarthritis (meniscal transection and anterior cruciate ligament rupture), NBQX reduced joint swelling, degeneration and pain, exceeding anti-degenerative effects of other drugs tested similarly. 3D osteocyte/osteoblast co-cultures and human bone samples taken from patients undergoing high tibial osteotomy joint realignment surgery, revealed underlying cellular mechanisms mediated by bone cells. Related drugs, already used in humans for epilepsy and migraine, represent a repurposing opportunity and are effective in our models of arthritis

Several previous pathoanatomical and biomechanical studies focused primarily on the cam morphology as the primary contributor to symptoms of femoroacetabular impingement (FAI) and limited range of motion. However, there is a growing population of individuals with asymptomatic cam morphologies who show no clinical signs; thus, the cam deformity, alone, may not fully delineate an individual's symptomatology or limited motion. These studies expanded beyond the cam morphology, to determine how additional anatomical characteristics could contribute to symptoms and influence functional mobility, using: 1) in vivo analyses, where we asked how specific anatomical parameters (in addition to the cam morphology) can predict individuals at risk of symptoms; 2) In silico simulations, where we examined how pathoanatomical features contributed to adverse loading conditions, resulting in higher risks of hip joint degeneration; 3) In vitro cadaveric experiments, where we examined the contributions of the cam morphology and encapsulating ligaments to joint mechanics and microinstability. This research further highlights that more emphasis should be placed on proper patient selection. There are implications of how structural anatomy can affect musculature, joint loading and stability, which should all be closely examined to improve the effectiveness of hip preservation surgery as well as the understanding of non-surgical management

Summary Statement. This project proves that Patellofemoral (PF) joint degeneration is not a contraindication to medial unicompartmental knee replacement. Introduction. Unicompartmental knee arthroplasty (UKA) is a recognised procedure for treatment of medial compartment osteoarthritis. Patellofemoral (PF) joint degeneration is widely considered to be a contraindication to medial unicompartmental knee replacement. We examined the validity of this preconception using information gathered prospectively on consecutive patients who underwent UKA using the Repicci II® UKA prosthesis for medial compartment osteoarthritis. Methods. We prospectively collected data on 147 consecutive patients who underwent the Repicci II® UKA for medial compartment osteoarthritis. All operations were performed between July 1999 and September 2000 by the same surgeon. The status of the PF joint was assessed intra-operatively in all patients, and accordingly patients were divided into two groups, one group with a normal PF joint, and the second group with degenerative changes of the PF joint. Variables measured for outcome included the International Knee Society (IKS) score, limb alignment, and range of motion. Radiographs were assessed for progression of disease or failure of implant. The mean follow-up was 9.4 years (range: 5–10.7 years). Patients were reviewed initially at 2 weeks, and then at 6 months post-operatively. They were subsequently reviewed on an annual basis.. All patients completed an IKS score preoperatively and at last follow-up. Age, gender, BMI, length of hospital stay, perioperative complications, all subsequent surgery, including revision of the prosthesis, and survivorship at 10 years was recorded, and results of the 2 groups compared. Results. A total of 147 patients were included in the study. None were lost to follow-up. Sixty nine had associated PF osteoarthritis (group A) while 78 patients had a normal PF compartment when assessed intra-operatively (group B). Post-operative outcomes of the two groups were compared using the ANCOVA analysis with adjustment for pre-operation values firstly, and adjusting also for gender, age, BMI and follow-up secondly. There were no significant differences in terms of IKS, alignment, and flexion between the two groups. However, patients in group B had significantly better extension post-operatively than patients in group A (p<0.05). Conclusion. We concluded that damage to the articular cartilage of the patellofemoral joint to the extent of full-thickness cartilage loss is not a contraindication to the Repicci II® unicondylar knee arthroplasty for medial compartment osteoarthritis. However, extension is significantly improved post-operatively in those patients with minimal or no PF joint degenerative disease

Background. Ankle fractures are often associated with ligamentous injuries of the distal tibiofibular syndesmosis, the deltoid ligament and are predictive of ankle instability, early joint degeneration and long-term ankle dysfunction. Detection of ligamentous injuries and the need for treatment remain subject of ongoing debate. In the classic article of Boden it was made clear that injuries of the syndesmotic ligaments were of no importance in the absence of a deltoid ligament rupture. Even in the presence of a deltoid ligament rupture, the interosseous membrane withstood lateralization of the fibula in fractures up to 4.5mm above the ankle joint. Generally, syndesmotic ligamentous injuries are treated operatively by temporary fixation performed with positioning screws. But do syndesmotic injuries need to be treated operatively at all?. Methods. The purpose of this biomechanical cadaveric study was to investigate the relative movements of the tibia and fibula, under normal physiological conditions and after sequential sectioning of the syndesmotic ligaments. Ten fresh-frozen below-knee human cadaveric specimens were tested under normal physiological loading conditions. Axial loads of 50 Newton (N) and 700N were provided in an intact state and after sequential sectioning of the following ligaments: anterior-inferior tibiofibular (AITFL), posterior-inferior tibiofibular (PITFL), interosseous (IOL), and whole deltoid (DL). In each condition the specimens were tested in neutral position, 10 degrees of dorsiflexion, 30 degrees of plantar flexion, 10 degrees of inversion, 5 degrees of eversion, and externally rotated up to 10Nm torque. Finally, after sectioning of the deltoid ligament, we triangulated Boden's classic findings with modern instruments. We hypothesized that only after sectioning of the deltoid ligament; the lateralization of the talus will push the fibula away from the tibia. Results. During dorsiflexion and external rotation the ankle syndesmosis widened, and the fibula externally rotated after sequential sectioning of the syndesmotic ligaments. After the AITFL was sectioned the fibula starts rotating externally. However, the external rotation of the fibula significantly reduced when the external rotation torque was combined with axial loading up to 700N as compared to the external rotation torque alone. The most relative moments between the tibia and fibula were observed after the deltoid ligament was sectioned. Conclusion. Significant increases in movements of the fibula relative to the tibia occur when an external rotation torque is provided. However, axial pressure seemed to limit external rotation because of the bony congruence of the tibiotalar surface. The AITFL is necessary to prevent the fibula to rotate externally when the foot is rotating externally. The deltoid ligament is the main stabilizer of the ankle mortise

Desiccation of articular cartilage during surgery is often unavoidable and may result in the death of chondrocytes, with subsequent joint degeneration. This study was undertaken to determine the extent of chondrocyte death caused by exposure to air and to ascertain whether regular rewetting of cartilage could decrease cell death. Macroscopically normal human cartilage was exposed to air for 0, 30, 60 or 120 minutes. Selected samples were wetted in lactated Ringer’s solution for ten seconds every ten or 20 minutes. The viability of chondrocytes was measured after three days by Live/Dead staining. Chondrocyte death correlated with the length of exposure to air and the depth of the cartilage. Drying for 120 minutes caused extensive cell death mainly in the superficial 500 μm of cartilage. Rewetting every ten or 20 minutes significantly decreased cell death. The superficial zone is most susceptible to desiccation. Loss of superficial chondrocytes likely decreases the production of essential lubricating glycoproteins and contributes to subsequent degeneration. Frequent wetting of cartilage during arthrotomy is therefore essential

Four-dimensional computed tomography (4DCT: three dimensional + time) allows to measure individual bone position over a period of time usually during motion. This method has been found useful in studying the joints around the wrist as dynamic instabilities are difficult to detect during static CT scans while they can be diagnosed using a 4DCT scan [1]–[3]. For the foot, the PedCAT system (Curvebeam, Warrington, USA) has been developed to study the foot bones under full weight bearing, however its use is limited to static images. On the contrary, dynamic measurements of the foot kinematics using skin markers can only describe motion of foot segments and not of individual bones. However, the ability to measure individual bone kinematics during gait is of paramount importance as such detailed information could be used to detect instabilities, to evaluate the effect of joint degeneration, to help in pre-operative planning as well as in post-operative evaluation. The overall gait kinematics of two healthy volunteers were measured in a gait analysis lab (Movement Analysis Lab Leuven, Belgium) using a detailed foot-model (Oxford foot model, [4]). The measured plantar-dorsiflexion and in-eversion were used to manipulate their foot during a 4D CT acquisition. The manipulation was performed through a custom made foot manipulator that controls the position and orientation of the foot bed according to input kinematics. The manipulator was compatible with the 4D CT Scanner (Aquilion One, Toshiba, JP), and a sequence of CT scans (37 CT scans over 10 seconds with 320 slices for each scan and a slice thickness of 0.5 mm) was generated over the duration of the simulation. The position of the individual bones was determined using an automatic segmentation routine after which the kinematics of individual foot bones were calculated. To do so, three landmarks were tracked on each bone over time allowing to construct bone-specific coordinate frames. The motion of the foot bed was compared against the calculated kinematics of the tibia-calcaneus as the angles between these two bones are captured with skin markers. There is high repeatability between the imposed plantar/dorsiflexion and inversion/eversion and the calculated. Although the internal/external rotation was not imposed, the calculated kinematics follow the same pattern as the measured in the gait-analysis lab. Based on the validation of the tibia-calcaneus, the kinematics were also calculated between four other joints: tibia-talar, talar-calcaneus, calcaneus-cuboid and talar-navicular. Repeatable measurements of individual foot bone motion were obtained for both volunteers. The use of 4D CT-scanning in combination with a foot manipulator can provide more detailed information than skin marker-based gait-analysis e.g. for the study of the the tibia-talar joint. In the future, the foot manipulator will be tested for its sensitivity for specific pathologies (e.g. metatarsal coalition) and will be further developed to better resemble a real-life stance phase of gait (i.e. to include isolated heel contact and toe off)

INTRODUCTION. Loss of joint function is only exploited in osteoarthritis (OA) once severe impairment is apparent. Animal models allow for lesion induction and serial OA progression measures. We recently described an adjustable non-surgical loading model for generating focal cartilage lesions in only the lateral femur joint compartment, in which regimes can be adjusted so that these either do or do not progress spontaneously. Herein, we use ventral plane videographic treadmill gait analysis to determine whether gait changes can be used to discriminate between stable and spontaneously progressing lesions, induced by these two loading regimes. METHODS. Animals encountered normal conditions, except during loading (9N, 40 cycles, 0.1 Hz, 10 sec/ cycle) which was applied to right knees in two groups (n=8) of 8-week-old male CBA mice: i) loaded once; ii) loaded 3 times/week for 2 weeks. Gait (including: brake, propel, stance, stride, stride length, stride frequency, steps and paw area) was assessed 3 times/week for 2 weeks in each mouse using a DigigaitTM treadmill. Thereafter, mice received 5mg/kg carprofen for analgesia and gait analysis repeated on 3 further alternate days. RESULTS. The two loading regimes produced virtually identical gait modifications with delayed onset (apparent on day 3) which remained unchanged for 2 weeks; mice loaded once only showed modified contralateral limb use, but those loaded multiply exhibited additional ipsilateral front limb modifications; no changes in gait were observed in loaded limbs. Intriguingly, the two regimes produced distinct responses to analgesia. Load-induced gait changes were completely rescued by carprofen in mice loaded only once, whilst those in mice loaded repetitively persisted. CONCLUSION. Our findings reveal specific and reproducible, compensatory changes in contralateral, non-loaded limb gait induced by any joint loading which produces focal articular lesions, and modified ipsilateral front limb use only when progressing lesions are induced by repetitive loading. We find that pain relief completely alleviates all gait modifications associated with stable lesions induced by single loading, but not those induced by repetitive loading. Differing responses in mice with stable and progressive articular cartilage load-induced lesions suggests that gait behaviour in a mechanical loading model of OA may predict joint degeneration

The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury.

Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline.

These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair.

Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative therapies. This paper summarises the syndromes of clinical OA in horses including pathogenesis, diagnosis and treatment, and details controlled studies of various treatment options using an equine model of clinical OA.

In a study on ten fresh human cadavers we examined the change in the height of the intervertebral disc space, the angle of lordosis and the geometry of the facet joints after insertion of intervertebral total disc replacements. SB III Charité prostheses were inserted at L3-4, L4-5, and L5-S1. The changes studied were measured using computer navigation sofware applied to CT scans before and after instrumentation.

After disc replacement the mean lumbar disc height was doubled (p < 0.001). The mean angle of lordosis and the facet joint space increased by a statistically significant extent (p < 0.005 and p = 0.006, respectively). By contrast, the mean facet joint overlap was significantly reduced (p < 0.001). Our study indicates that the increase in the intervertebral disc height after disc replacement changes the geometry at the facet joints. This may have clinical relevance.

The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture.

The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone.