Bardoxolone methyl ameliorates osteoarthritis by inhibiting osteoclastogenesis and protecting the extracellular matrix against degradation.

Inflammation and oxidative damage are closely related to the development of osteoarthritis. Bardoxolone methyl (CDDO-Me), a semisynthetic oleanane triterpenoid, plays a strong anti-inflammatory and antioxidant role. The purpose of our research was to explore fundamental mechanisms of CDDO-Me in orthopaedics development. The results showed that CDDO-Me inhibited nuclear factor-κB ligand (RANKL)-induced osteoclast formation and extracellular matrix (ECM) degradation by activating the Nrf2/HO-1 signaling pathways and inhibiting NF-κB pathway activation and excess ROS production. In vivo, CDDO-Me significantly attenuated articular cartilage proteoglycan loss and the number of TRAP-positive osteoclasts in a destabilized medial meniscus (DMM) mouse model of OA. Taken together, these data demonstrate that CDDO-Me inhibits osteoclastogenesis and ECM degradation, underscoring its potential therapeutic value in treating OA.