Nrf2/ARE is a key pathway for curcumin-mediated protection of TMJ chondrocytes from oxidative stress and inflammation

Temporomandibular joint osteoarthritis (TMJ OA) is a complex multifactorial disease that can be induced by inflammation and oxidative stress. Curcumin has been reported to have anti-inflammatory and antioxidant properties. Herein, the anti-inflammatory and antioxidant mechanisms of curcumin in TMJ OA were investigated. Curcumin treatment inhibited the expression of the inflammation mediators IL-6, iNOS, and COX-2 and of the matrix-degrading proteinases MMP-1, MMP-3, MMP-9, MMP-13, ADAMTS-4, and ADAMTS-5 and upregulated the mRNA levels of the cartilage anabolic factors COL2A1 and ACAN after IL-1 beta treatment. Curcumin treatment also decreased oxidative stress injury following IL-1 beta stimulation. Pathway analysis demonstrated that the ROS/Nrf2/HO-1-SOD2-NQO-1-GCLC signaling axis is a key axis through which curcumin activates the Nrf2/ARE pathway in TMJ inflammatory chondrocytes. Curcumin-induced anti-inflammatory and cartilage protective effects were significantly abrogated by specific Nrf2 siRNA. In vivo results demonstrated that curcumin treatment protected TMJ articular cartilage from progressive degradation. Our experimental results indicate that curcumin inhibits inflammation, oxidative stress, and the matrix degradation of TMJ inflammatory chondrocytes through the Nrf2/ARE signaling pathway, thereby exerting cartilage protective effects. This study provides insight into potential therapeutic approaches for TMJ OA.