Inhibition of NCOA4 attenuates ferroptosis and oxidative stress in chondrocytes

Osteoarthritis (OA) is a degenerative joint disease characterized by chronic inflammation, oxidative stress, and cartilage degradation. Recent studies suggest that ferroptosis, an iron-dependent form of regulated cell death, may contribute to OA pathogenesis. In this study, we performed transcriptomic analysis using publicly available synovial tissue data from OA patients. The results revealed a consistent downregulation of key ferroptosis-inhibitory genes (GPX4, FTH1, and SLC7A11) and upregulation of NCOA4, a critical mediator of ferritinophagy. These findings suggest that ferroptosis and oxidative stress are actively involved in the molecular landscape of OA synovium. Gene expression patterns also indicated elevated oxidative stress and inflammation, reflected by the upregulation of proinflammatory cytokines and matrix metalloproteinases. Taken together, our results highlight NCOA4-mediated ferroptosis as a potential contributor to OA development and suggest that targeting ferroptosis pathways may offer novel therapeutic strategies for OA.