The role of ferroptosis in osteoarthritis: Progress and prospects.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, marked by cartilage degeneration, synovitis, and subchondral bone changes. The absence of effective drugs and treatments to decelerate OA's progression highlights a significant gap in clinical practice. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has emerged as a research focus in osteoarthritic chondrocytes. This form of cell death is characterized by imbalances in iron and increased lipid peroxidation within osteoarthritic chondrocytes. Key antioxidant mechanisms, such as Glutathione Peroxidase 4 (GPX4) and the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) pathway, are vital in countering ferroptosis in osteoarthritic chondrocytes. This review collates recent findings on ferroptosis in osteoarthritic chondrocytes, emphasizing iron regulation, lipid peroxidation, and antioxidative responses. It also explores emerging therapeutics aimed at mitigating OA by targeting ferroptosis in chondrocytes.