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

Xia Zhao1, Yixue Peng2, Mengsong Wang3, Qishuang Tan4

1Institute of Respiratory and Co-occurring Diseases, West China Hospital of Sichuan University, Chengdu, China
2Anaesthesia Surgery Centre, West China Hospital of Sichuan University, Chengdu, China
3Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China
4Research Base, West China Hospital of Sichuan University, Chengdu, China

Keywords: Cartilage injury, ferroptosis, METTL3, osteoarthritis, PRDX3

Abstract

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.

Cite this article as: Zhao X, Peng Y, Wang M, Tan Q. Methylation of PRDX3 expression alleviate ferroptosis and oxidative stress in patients with osteoarthritis cartilage injury. ArchRheumatol. 2025;40(2): 197-210.