Receptor-interacting protein 1 inhibition prevents mechanical stress-induced temporomandibular joint osteoarthritis by regulating apoptosis and later-stage necroptosis of chondrocytes.

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJ OA) is a common degenerative joint disease that has multiple causes. The abnormal stress distribution is known to be an important trigger of TMJ OA. This article explored the pathological changes of the condylar cartilage under 60 g mechanical force and whether the inhibition of Receptor-interacting protein 1 (RIP1) can protect stress-induced TMJ OA.

MATERIAL AND METHODS: We used a compressive mechanical force-induced-TMJ OA model and Lenti-virus targeting RIP1 to perform this study. A total of 72 male rats were used in the animal experiment. Each rat was injected with a negative control Lenti-shRNA in the right TMJ and Lenti-siRIP1 in the left TMJ and euthanized after 4 and 7 days, respectively. Quantitative real-time PCR, immunohistochemistry, Tunnel staining and Micro-CT were used to detect cartilage pathological changes and one way ANOVA with LSD analysis was used to determine statistical significance between groups.

RESULTS: The results identified the characteristics of the spatio-temporal changes in stress-induced TMJ OA. Under mechanical force, inflammation and apoptosis, which occur in the whole layer of mandibular cartilage, appear on the 4th day and persist till the 7th day. Necroptosis arises in the later stage of mechanical force and is mainly located in the transition layer. RIP1 inhibition through Lenti-virus could protect stress-induced mandibular cartilage thinning by inhibiting persisted apoptosis and later-stage necroptosis in the transition layer.

CONCLUSIONS: RIP1 plays an essential role in the destruction of mandibular cartilage under mechanical force. RIP1 inhibition through Lenti-virus could protect mechanical stress-induced TMJ OA.