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

作者：Xuchang Zhou, Yajing Yang, Qiu Xu, Huili Deng, Hong Cao, Tao Liao, Xier Chen, Caihua Huang, Donghai Lin, Guoxin Ni · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.010 · 被引用次数：24 · 研究领域：Osteoarthritis Treatment and Mechanisms、Aldose Reductase and Taurine、Pharmacological Effects and Assays

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 demonstr...