Original Article

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

Volume 40 · Issue 2 Publish Date: June 30, 2025
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DOI
Xia Zhao ORCID
Institute of Respiratory and Co-occurring Diseases, West China Hospital of Sichuan University, Chengdu, China image/svg+xml
Yixue Peng ORCID
Anaesthesia Surgery Centre, West China Hospital of Sichuan University, Chengdu, China image/svg+xml
Mengsong Wang ORCID
Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China image/svg+xml
Qishuang Tan ORCID
Research Base, West China Hospital of Sichuan University, Chengdu, China image/svg+xml
Xia Zhao, Yixue Peng, Mengsong Wang, & Qishuang Tan. (2025). Methylation of PRDX3 Expression Alleviate Ferroptosis and Oxidative Stress in Patients with Osteoarthritis Cartilage Injury. Archives of Rheumatology, 40(2), 197–210. https://doi.org/10.5152/ArchRheumatol.2025.11031
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Abstract

Background/Aims: Osteoarthritis features cartilage degeneration, synovial fibrosis, and bone remodeling. Long-term Western therapies may worsen cartilage damage. We investigated PRDX3’s role in ferroptosis and oxidative stress in osteoarthritis cartilage injury.

Materials and Methods: In osteoarthritis models, PRDX3 expression was downregulated. Single-cell analysis showed PRDX3 in patient bone cells.

Results: Sh-PRDX3 promoted cartilage injury via oxidative stress induction. PRDX3 suppressed ROS accumulation and mitochondria-dependent ferroptosis in vitro and mouse models. PRDX3 induced SIRT3 to reduce SIRT3 ubiquitination. METTL3-mediated m6A modification decreased PRDX3 mRNA stability via YTHDF1.

Conclusion: METTL3-mediated m6A decreases PRDX3 mRNA stability to relieve ferroptosis and oxidative stress in osteoarthritis models. Targeting METTL3 may be therapeutic.

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Article Info
Published In
Journal Archives of Rheumatology
Volume / Issue Volume 40 · Issue 2
Pages 197-210
History
Published Online June 30, 2025
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Affiliations
Xia Zhao ORCID
Institute of Respiratory and Co-occurring Diseases, West China Hospital of Sichuan University, Chengdu, China
Yixue Peng ORCID
Anaesthesia Surgery Centre, West China Hospital of Sichuan University, Chengdu, China
Mengsong Wang ORCID
Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China
Qishuang Tan ORCID
Research Base, West China Hospital of Sichuan University, Chengdu, China
Cite this Article
Xia Zhao, Yixue Peng, Mengsong Wang, & Qishuang Tan. (2025). Methylation of PRDX3 Expression Alleviate Ferroptosis and Oxidative Stress in Patients with Osteoarthritis Cartilage Injury. Archives of Rheumatology, 40(2), 197–210. https://doi.org/10.5152/ArchRheumatol.2025.11031
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