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ObjectiveThe mechanisms linking obesity and osteoarthritis (OA) are not fully understood and have been generally attributed to increased weight, rather than metabolic or inflammatory factors. Here, we examined the influence of fatty acids, adipokines, and body weight on OA following joint injury in an obese mouse model.MethodsMice were fed high-fat diets rich in various fatty acids (FA) including saturated FAs (SFAs), ω-6 polyunsaturated FAs (PUFAs), and ω-3 PUFAs. OA was induced by destabilising the medial meniscus. Wound healing was evaluated using an ear punch. OA, synovitis and wound healing were determined histologically, while bone changes were measured using microCT. Activity levels and serum cytokines were measured at various time-points. Multivariate models were performed to elucidate the associations of dietary, metabolic and mechanical factors with OA and wound healing.ResultsUsing weight-matched mice and multivariate models, we found that OA was significantly associated with dietary fatty acid content and serum adipokine levels, but not with body weight. Furthermore, spontaneous activity of the mice was independent of OA development. Small amounts of ω-3 PUFAs (8% by kcal) in a high-fat diet were sufficient to mitigate injury-induced OA, decreasing leptin and resistin levels. ω-3 PUFAs significantly enhanced wound repair, SFAs or ω-6 PUFAs independently increased OA severity, heterotopic ossification and scar tissue formation.ConclusionsOur results indicate that with obesity, dietary FA content regulates wound healing and OA severity following joint injury, independent of body weight, supporting the need for further studies of dietary FA supplements as a potential therapeutic approach for OA.

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

Objective To determine whether there is a correlation between the degree of the tibial plateau angle (TPA) and the incidence of medial meniscal tear (MMT) in dogs with complete cranial cruciate ligament (CCL) rupture observed at the time of arthrotomy. Methods 144 dogs met the inclusion criteria for this study with 88 (61.11%) found to have a MMT. Breed, age, sex, weight, affected limb, duration of lameness, and the integrity of contralateral stifle were recorded. Six groups were established based on TPA ranges measured in degrees. Results There was a one-fourth reduction in the number of MMT observed in dogs with a TPA between 35 to 37 degrees and an almost two-fold reduction in the number of MMT in dogs with a TPA greater than 38 degrees. There was a 6 times greater risk of MMT in those with acute lameness in comparison to those with a chronic lameness. Conclusion A relationship was found to exist between MMT and TPA with a lower prevalence of MMT in dogs with an excessive TPA. Chronic lameness was also associated with a lower prevalence of MMT regardless of TPA degree. In dogs with complete CCL tears, excessive TPA and chronic lameness were found to be statistically significant in relation to fewer MMT.

Objectives In osteoarthritis (OA) chondrocytes surrounding lesions express elevated bone morphogenetic protein 2 (BMP2) levels. To investigate the functional consequence of chondrocyte-specific BMP2 expression, we made a collagen type II dependent, doxycycline (dox)-inducible BMP2 transgenic mouse and studied the effect of elevated BMP2 expression on healthy joints and joints with experimental OA. Methods We cloned a lentivirus with BMP2 controlled by a tet-responsive element and transfected embryos of mice containing a collagen type II driven cre-recombinase and floxed rtTA to gain a mouse expressing BMP2 solely in chondrocytes and only upon dox exposure (Col2-rtTA-TRE-BMP2). Mice were treated with dox to induce elevated BMP2 expression. In addition, experimental OA was induced (destabilisation of the medial meniscus model) with or without dox supplementation and knee joints were isolated for histology. Results Dox treatment resulted in chondrocyte-specific upregulation of BMP2 and severely aggravated formation of osteophytes in experimental OA but not in control mice. Moreover, elevated BMP2 levels did not result in alterations in articular cartilage of young healthy mice, although BMP2-exposure did increase VDIPEN expression in the articular cartilage. Strikingly, despite apparent changes in knee joint morphology due to formation of large osteophytes there were no detectible differences in articular cartilage: none with regard to structural damage nor in Safranin O staining intensity when comparing destabilisation of the medial meniscus with or without dox exposure. Conclusions Our data show that chondrocyte-specific elevation of BMP2 levels does not alter the course of cartilage damage in an OA model in young mice but results in severe aggravation of osteophyte formation.

A patellar luxation and concomitant cranial cruciate ligament rupture is a common pathology in dogs. Diagnosis is based on clinical evidence of a patellar luxation and stifle joint instability. However, diagnostic imaging is required to assess the number of skeletal deformities and signs of instability. Surgical options include both soft tissue and osseous techniques, although, in most cases, a combination of multiple procedures is necessary to correct the patellar luxation and restore the stifle joint stability. Complication rates are generally low, but can include reluxation and implant-associated complications. This article describes the patellar luxation and cranial cruciate ligament rupture signs in dogs, including the clinical presentation and diagnosis, and discusses current treatment options.

Purpose The geometry of the trochlear groove is considered to be an important determinant in the pathogenesis of the patellofemoral joint disorders. However, the effect of patellar position during the development of the femoral trochlear groove is unclear. This animal study aimed to investigate the relationship between the position of the patella and development of the femoral trochlear groove in growing rabbits. Methods Thirty-two knees from 16 rabbits were included in this study and were divided into two groups. First group consisted of the left knees and was used as a control group with no surgical interventions. The second group involved the right knees on which patellar tendon Z-plasty lengthening was performed to cause patellar malposition (patella alta) before 1 month of age. Computed tomographic (CT) evaluations of both knees were obtained when the animals were 1 month age before the surgical intervention and also at 6 months after the surgical intervention. Angle and depth measurements were acquired from the proximal, middle, and distal reference points along the femoral trochlear groove. After the CT scan acquisition at 6 months following the surgical procedures, rabbits were killed and additional measurements of the trochlear groove angles were performed manually. Results The mean middle and distal trochlear groove angles for the experiment group with patella alta were significantly higher compared to that of control group ( p  < 0.017). The increase in mean trochlear depth for the animals in the control group was found to be significantly higher compared to experiment group at the distal zone ( p  < 0.017). Conclusion Distal femoral groove with an inadequately positioned patella becomes more flattened and this may be a predisposing factor for patellar instability. Level of evidence Controlled laboratory study, Level II.

Purpose The geometry of an articular surface is an important determinant of joint function. Although the geometry of the trochlear groove is considered to be important in the pathogenesis of patellofemoral joint disorders, the effects of the patella during the development of the femoral trochlear groove are unclear. This animal study aimed to investigate the relationship between the position of the patella and development of femoral trochlear groove in growing rabbits. Methods Twenty-four knees of 12 rabbits were included in this study and were divided into two groups. First group consisted of the left knees and was used as the control group to which no surgical procedures were applied. Second group involved the right knees to which medial soft tissue restraints release was applied before 1 month of age. Computed tomographic (CT) evaluation of both knees of each rabbit was made in their first month of age before medial retinacular release and also during post-op 1-year follow-up. CT measurements included both the angle and depth of the femoral trochlear groove from 3 different parts (proximal, middle and distal) of the distal femur, and then these measurements were averaged. Results Measurements revealed that while in the control group the groove angle decreased 27.4 degrees and the depth increased 0.11 mm, in the operated counterparts groove angle decreased 16.8 degrees and groove depth increased 0.03 mm, which indicated the flattening of the femoral groove in the operated group. These differences were found to be statistically significant ( P  < 0.05). Conclusion The results indicated that distal femoral groove with inadequate patellar position becomes more flattened and causes predisposition for patellar instability. Consequently, the clinical relevance of this study was that early reconstruction of the patellofemoral joint should be performed in the childhood to prevent the patellofemoral problems that are likely to be encountered in the following years. Level of evidence Prospective comparative study, Level II.

Cranial cruciate ligament rupture (CR) is a degenerative condition in dogs that typically has a non-contact mechanism. Subsequent contralateral rupture often develops in dogs with unilateral CR. Synovitis severity is an important factor that promotes ligament degradation. Consequently, we wished to evaluate the utility of arthroscopy for assessment of stifle synovitis in dogs with CR. Herein, we report results of a prospective study of 27 dogs with unilateral CR and bilateral radiographic osteoarthritis. Arthroscopic images and synovial biopsies from the lateral and medial joint pouches were obtained bilaterally and graded for synovial hypertrophy, vascularity, and synovitis. Synovial tartrate-resistant acid phosphatase-positive (TRAP+) macrophages, CD3(+) T lymphocytes, Factor VIII+ blood vessels, and synovial intima thickness were quantified histologically and related to arthroscopic observations. Risk of subsequent contralateral CR was examined using survival analysis. We found that arthroscopic scores were increased in the index stifle, compared with the contralateral stifle (p<0.05). Numbers of CD3+ T lymphocytes (SR = 0.50, p<0.05) and TRAP+ cells in joint pouches (SR = 0.59, p<0.01) were correlated between joint pairs. Arthroscopic grading of vascularity and synovitis was correlated with number density of Factor VIII+ vessels (SR>0.34, p<0.05). Arthroscopic grading of villus hypertrophy correlated with numbers of CD3(+) T lymphocytes (SR = 0.34, p<0.05). Synovial intima thickness was correlated with arthroscopic hypertrophy, vascularity, and synovitis (SR>0.31, p<0.05). Strong intra-observer and moderate inter-observer agreement for arthroscopic scoring was found. Dog age and arthroscopic vascularity significantly influenced risk of contralateral CR over time. We conclude that arthroscopic grading of synovitis is a precise tool that correlates with histologic synovitis. Arthroscopy is useful for assessment of stifle synovitis in client-owned dogs, and could be used in longitudinal clinical trials to monitor synovial responses to disease-modifying therapy.

Osteoarthritis (OA) is a chronic, degenerative disease affecting the articular cartilage and subchondral bone that causes pain and inhibits movement. The stifle’s joint fibrous capsule contains the synovial membrane, which produces cartilage nutrients. A ruptured cranial cruciate ligament injures the joint and produces OA. Osteoarthritis diagnosis starts with clinical radiographic and ultrasonographic tests, although the latter is not used very much in dog and cat clinics for this purpose. The objective of this study was to establish the correlation among the results of orthopedic, radiographic, ultrasonographic examinations and structural anatomical changes revealed by arthroscopic evaluation to diagnose stifle joint OA and determine risk factors in the dogs affected. Of 44 clinical cases of OA included in the study, 88.64% had ruptured of cranial cruciate ligaments. The correlation between synovial fluid effusion and osteophytosis was of 0.84. It was concluded that there is good diagnostic agreement between synovial fluid effusion and osteophytosis when dealing with stifle joint OA. Risk factors for dogs regarding the development of stifle joint OA included: ruptured cranial cruciate ligaments or patella luxation, female dogs and weight over 10 kg.

Objective Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degradation driven by matrix‐degrading enzymes. Reproducible ex vivo models are essential for studying early degenerative processes and evaluating potential therapeutics. However, there remains a lack of accessible, cost‐effective models that accurately replicate the biochemical environment and early‐stage damage of OA. This study aimed to develop and validate a bovine cartilage explant model that replicates key features of early OA through enzymatic induction of tissue damage. Methods Bovine stifle cartilage explants were exposed to combinations of matrix metalloproteinases, aggrecanases, and cartilage biomarkers. Tissue damage was evaluated histologically, and semiquantitative scoring was used to assess structural changes. Statistical analyses were conducted to determine differences between treatment groups. Results Enzyme‐treated samples exhibited significantly greater cartilage degradation compared to controls. The addition of cartilage oligomeric matrix protein (COMP) increased tissue damage, suggesting an active role in matrix destabilization. In contrast, the inclusion of TIMP‐3, a known protease inhibitor, did not reduce degradation, raising questions about its protective efficacy in this context. Conclusion This chemically induced bovine model successfully simulates early cartilage degeneration consistent with OA pathology. Supported by recent literature on the roles of MMPs, ADAMTS‐5, and COMP in joint disease, the model offers a valuable platform for future studies on OA mechanisms and therapeutic screening. A bovine cartilage explant model was developed to simulate early osteoarthritis using matrix‐degrading enzymes. Histological analysis revealed synergistic cartilage damage from MMPs, ADAMTS‐5, and COMP. This ex vivo model offers a reproducible platform to study OA mechanisms and test therapeutic interventions.