| Knee osteoarthritis (KOA) is a chronic degenerative joint disease characterized by articular cartilage degeneration, subchondral bone changes, and synovial inflammation, accompanied by joint pain and dysfunction. Nrf2 (nuclear factor erythroid 2-related factor 2) is an important antioxidant regulator in cells. It plays a key role in maintaining cell redox balance and protecting tissue function by regulating the expression of downstream antioxidant, anti-inflammatory, and anti-ferroptosis genes. Studies have shown that Nrf2 signaling pathway plays a protective role in the pathogenesis of KOA through a variety of mechanisms. After activation of Nrf2, it can reduce ROS accumulation, alleviate oxidative stress, and protect chondrocytes from oxidative damage by up-regulating the expression of antioxidant enzymes such as HO-1, NQO1, and SOD. Nrf2 attenuates synovial inflammation and cartilage degeneration by inhibiting the activation of NF-κB and NLRP3 inflammasome, reducing the production of pro-inflammatory factors (such as IL-1β, TNF-α). In addition, Nrf2 protects chondrocytes by regulating GPX4 expression, inhibiting lipid peroxidation and ferroptosis, and further delaying KOA. This review systematically summarizes the specific mechanisms of Nrf2 signaling pathway in anti-oxidation, anti-inflammatory, and anti-ferroptosis in KOA, discusses its core role and therapeutic potential in KOA, and emphasizes the effects of these mechanisms alone or in interaction on KOA. It provides a new perspective for understanding the pathogenesis of KOA, and provides a theoretical basis and research direction for the development of multi-target intervention strategies and efficient treatment methods for KOA. |