Methylation of PRDX3 Expression Alleviate Ferroptosis and Oxidative Stress in Patients with Osteoarthritis Cartilage Injury.

Background/Aims: Osteoarthritis typically features cartilage degeneration, synovial fibrosis, and bone remodeling. While clinical Western medicine therapies can restore joint functions, long-term use may exacerbate cartilage damage. This study was designed to investigate the impact of peroxiredoxin 3 (PRDX3) on ferroptosis and oxidative stress in osteoarthritis cartilage injury and its potential mechanism. Materials and Methods: In the osteoarthritis model, the expression of PRDX3 was downregulated. Single-cell analysis revealed that the PRDX3 gene was expressed in bone cells of osteoarthritis patients. Results: Sh-PRDX3 promoted osteoarthritis cartilage injury in the mouse model via the induction of oxidative stress. PRDX3 suppressed reactive oxygen species accumulation and mitochondria-dependent ferroptosis in the in vitro model or mice model of osteoarthritis. PRDX3 induced SIRT3 to reduce SIRT3 ubiquitin. Moreover, METTL3-mediated m6A modification decreases PRDX3 mRNA stability by YTHDF1 in the osteoarthritis cartilage injury model. Conclusion: These findings indicate that METTL3-mediated m6A modification decreases PRDX3 mRNA stability to relieve ferroptosis and oxidative stress in the model of osteoarthritis cartilage injury in a YTHDF1-dependent manner. Targeting METTL3 is thus a potentially effective therapeutic strategy for patients with osteoarthritis cartilage injury.