Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling in osteoarthritis induced by anterior cruciate ligament transection

Xuchang Zhou; Yajing Yang; Xu Qiu; Huili Deng; Hong Cao; Tao Liao; Xier Chen; Caihua Huang; Donghai Lin; Guoxin Ni

doi:10.1016/j.jare.2025.01.010

Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling in osteoarthritis induced by anterior cruciate ligament transection

J Adv Res. 2025 Jan 6:S2090-1232(25)00029-3. doi: 10.1016/j.jare.2025.01.010. Online ahead of print.

Authors

Xuchang Zhou¹, Yajing Yang², Xu Qiu³, Huili Deng¹, Hong Cao⁴, Tao Liao⁵, Xier Chen¹, Caihua Huang⁶, Donghai Lin⁷, Guoxin Ni⁸

Affiliations

¹ Department of Rehabilitation Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China.
² Department of Acupuncture and Moxibustion, Hubei University of Chinese Medicine, Wuhan 430070, China.
³ Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
⁴ Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Shenzhen 518055, China.
⁵ Department of Rehabilitation Medicine, Chengdu Second People's Hospital, Chengdu 610000, China.
⁶ Research and Communication Center of Exercise and Health, Xiamen University of Technology, Xiamen 361024, China.
⁷ Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China. Electronic address: [email protected].
⁸ Department of Rehabilitation Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China. Electronic address: [email protected].

PMID: 39778769
DOI: 10.1016/j.jare.2025.01.010

Abstract

Objective: The aim of this study was to investigate the potential molecular mechanisms by which taurine protects against cartilage degeneration.

Methods: The anterior cruciate ligament transection (ACLT) surgery was used to construct an animal model of osteoarthritis (OA). Metabolomics was used to identify characteristic metabolites in osteoarthritic chondrocytes. Transcriptomics and metabolomics were used to explore potential mechanisms by which the small molecule metabolite taurine protects against inflammatory chondrocyte damage. Cell transfection and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects inflammatory chondrocytes in vitro. Finally, adeno-associated virus and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects against cartilage degeneration in vivo.

Results: Metabolomic assays identified taurine as a possible key metabolic molecule in the progression of OA. Transcriptomics and metabolomics revealed that O-GlcNAc transferase (OGT)-dependent O-GlcNAcylation and Gpx4-dependent ferroptosis may mediate the inflammatory protective effects of taurine on chondrocytes, which was further confirmed by gain and loss of function in vitro. Subsequently, further experiments indicated that the possible existence of a direct binding site for Gpx4 and OGT proteins, which provides evidence for the presence of O-GlcNAc modification of Gpx4 protein. Finnaly, we demonstrated that Gpx4-dependent ferroptosis and OGT-dependent O-GlcNAcylation may be potential mechanisms by which taurine protects against cartilage degeneration in vivo.

Conclusion: Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling. Supplementation with taurine, a safe nonessential amino acid, may be a potential therapeutic strategy for OA.

Keywords: Ferroptosis; O-GlcNAcylation; Osteoarthritis; Oxidative stress; Taurine.