Salubrinal alleviates cartilage degradation in a rabbit temporomandibular joint osteoarthritis model

To investigate and explain the beneficial effects of local intra-articular injection of Salubrinal on temporomandibular joint osteoarthritis (TMJOA) using a rabbit model of anterior disc displacement (ADD).Rabbits were divided and subjected to surgical ADD. Salubrinal was administered by intra-articular injection in the TMJ every other day for 2 and 4 weeks after operation. Histological examination and TUNEL staining were then performed. Immunohistochemistry, quantitative real-time PCR, and Western blot analysis were employed to evaluate the expression of endoplasmic reticulum (ER) stress-related markers, catabolic factors, extracellular matrix proteins, inflammatory factors, and nuclear factor-kappa B (NF-κB) activation.In the ADD groups, we found that Salubrinal partly reversed condylar cartilage deterioration according to the histological analysis. Salubrinal reduced chondrocytes apoptosis while increased matrix components including Collagen II and Aggrecan. Meanwhile, Salubrinal downregulated the catabolic expression of MMP13, ADAMTS5, VEGF, TNF-α, and IL-1β. We also observed that Salubrinal inhibited ER stress activation by reducing the expression of GRP78, CHOP, ATF4, and Caspase-12. Additionally, Salubrinal suppressed the phosphorylation of NF-κB.These results indicate that Salubrinal alleviates cartilage degradation following ADD, suggesting that intra-articular injection of Salubrinal is a potential therapeutic approach for preventing TMJOA.