Elucidating the mechanism of taurine in alleviating osteoarthritis progression based on bioinformatics, machine...

Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, plays a pivotal role in chondrocyte death and the pathogenesis of osteoarthritis (OA). Taurine, a sulfur-containing amino acid with established anti-inflammatory and anti-ferroptotic properties, has been implicated in joint protection; however, its potential to mitigate OA progression by targeting ferroptosis mechanisms remains largely unexplored.

RNA sequencing was performed on normal and OA knee joint cartilage tissues to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was used to screen for OA-related modules, and ferroptosis-related targets were retrieved from public databases. Intersecting genes from the DEGs, WGCNA modules, and ferroptosis targets underwent pathway enrichment analysis. Taurine target genes were predicted via multiple databases, and machine learning algorithms were applied to identify hub genes. A nomogram model was constructed to evaluate diagnostic accuracy. Immune infiltration was assessed using the CIBERSORT algorithm. Furthermore, in vitro experiments involving interleukin-1 beta (IL-1β)-stimulated chondrocytes and in vivo studies using a destabilization of the medial meniscus (DMM) mouse model were conducted to validate the effects of taurine.

Machine learning analysis identified four key hub genes: CSRNP1, CTH, OSBPL3, and CITED2. CTH was selected as the primary focus due to the effect of taurine on its expression in IL-1β-stimulated chondrocytes. In vitro assays demonstrated that taurine treatment specifically reversed the IL-1β-induced downregulation of CTH. Mechanistic studies showed that taurine directly bound to the CTH protein and attenuated IL-1β-induced ferroptosis by restoring CTH expression, thereby increasing glutathione (GSH) levels, reducing iron accumulation and lipid peroxidation, and upregulating solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Consistently, taurine alleviated cartilage degradation and synovial inflammation in DMM-induced OA mice, whereas these benefits were reversed by the CTH inhibitor propargylglycine (PAG).

Taurine exerted significant chondroprotective effects, at least in part, by directly targeting CTH to suppress chondrocyte ferroptosis, thereby ameliorating OA progression.