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Background: Temporomandibular joint osteoarthritis (TMJ‐OA) causes severe symptoms such as chewing difficulties, acute pain and even maxillofacial deformity. However, there is hardly any effective disease‐curing strategy because of uncertainty in aetiology. Animal model is an excellent tool to investigate the mechanism, prevention and treatment on diseases. Currently, although several TMJ‐OA animal models have been established, there are almost no comparative studies on different models, which poses a great challenge for selecting suitable models. Objective: To compare three TMJ‐OA induction methods and assess their applicability considering pathological changes in the cartilage, subchondral bone, osteoclasts, and synovium. Methods: Murine models were employed and followed for 3 and 6 weeks after experimental procedures (surgery, injection, crossbite). The TMJ changes were evaluated by Safranin‐O/Fast green staining, immunofluorescence staining, micro‐CT, TRAP staining, and HE staining. Results: In the Surgery group, a pronounced drop in bone volume fraction was observed. In the Injection group, chondrocytes were mostly disordered or arranged in clusters and a substantial increase in the OARSI score and osteoclasts was found. The OARSI score and osteoclasts also increased significantly in the Crossbite group, although to a lower extent compared with injection. Conclusion: Osteoarthritis‐like changes were observed in all models. Concerning the applicability of the different induction methods, surgery might be an important resource for the assessment of post‐traumatic TMJ‐OA and subchondral bone changes in early stages. Injection induces a severe end‐stage osteoarthritis in a short time and provides model basis for advanced TMJ‐OA. Crossbite might be more reasonable model to explore the pathogenesis mechanism of temporomandibular arthritis due to occlusal disorders. [ABSTRACT FROM AUTHOR]

Objectives: Chondrocyte ferroptosis contributes to osteoarthritis (OA) progression, and D‐mannose shows therapeutic value in many inflammatory conditions. Here, we investigated whether D‐mannose interferes in chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration. Materials and methods: In vivo anterior cruciate ligament transection (ACLT)‐induced OA mouse model and an in vitro study of chondrocytes in an OA microenvironment induced by interleukin‐1β (IL‐1β) exposure were employed. Combined with Epas1 gene gain‐ and loss‐of‐function, histology, immunofluorescence, quantitative RT‐PCR, Western blot, cell viability and flow cytometry experiments were performed to evaluate the chondroprotective effects of D‐mannose in OA progression and the role of hypoxia‐inducible factor 2 alpha (HIF‐2 α) in D‐mannose‐induced ferroptosis resistance of chondrocytes. Results: D‐mannose exerted a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and alleviated OA progression. HIF‐2α was identified as a central mediator in D‐mannose‐induced ferroptosis resistance of chondrocytes. Furthermore, overexpression of HIF‐2α in chondrocytes by Ad‐Epas1 intra‐articular injection abolished the chondroprotective effect of D‐mannose during OA progression and eliminated the role of D‐mannose as a ferroptosis suppressor. Conclusions: D‐mannose alleviates osteoarthritis progression by suppressing HIF‐2α‐mediated chondrocyte sensitivity to ferroptosis, indicating D‐mannose to be a potential therapeutic strategy for ferroptosis‐related diseases. [ABSTRACT FROM AUTHOR]