biostudies-literatureUnknown16Wang J<h4>Introduction</h4>Osteoarthritis (OA) is a degenerative joint disease marked by chronic inflammation, extracellular matrix degradation, and dysregulated cell death. The roles of apoptosis-, autophagy-, and ferroptosis-related genes in OA pathogenesis remain unclear.<h4>Methods</h4>Integrated bioinformatics analyses were conducted on public GEO datasets to identify apoptosis-autophagy-ferroptosis-related genes (AAFRGs). TLR3 and GLUL were identified using LASSO, random forest, and SVM-RFE algorithms. Immune infiltration analysis, immunohistochemistry, and functional assays in human chondrocytes were performed, and ACLT-induced rat OA models were used for <i>in vivo</i> validation.<h4>Results</h4>TLR3 was upregulated and associated with pro-inflammatory immune cells, while GLUL was downreFrontiers in immunology1650375https://www.ebi.ac.uk/biostudies/studies/S-EPMC12875911biostudies-literatureTLR3 and GLUL orchestrate inflammatory and homeostatic imbalance in osteoarthritis.PMC12875911Peng PXu SQin YWang JChen BWang KfalseTLR3 and GLUL orchestrate inflammatory and homeostatic imbalance in osteoarthritis.<h4>Introduction</h4>Osteoarthritis (OA) is a degenerative joint disease marked by chronic inflammation, extracellular matrix degradation, and dysregulated cell death. The roles of apoptosis-, autophagy-, and ferroptosis-related genes in OA pathogenesis remain unclear.<h4>Methods</h4>Integrated bioinformatics analyses were conducted on public GEO datasets to identify apoptosis-autophagy-ferroptosis-related genes (AAFRGs). TLR3 and GLUL were identified using LASSO, random forest, and SVM-RFE algorithms. Immune infiltration analysis, immunohistochemistry, and functional assays in human chondrocytes were performed, and ACLT-induced rat OA models were used for <i>in vivo</i> validation.<h4>Results</h4>TLR3 was upregulated and associated with pro-inflammatory immune cells, while GLUL was downre2025-01-01T00:00:00Z20252026-07-05T03:14:55.4Z2026-07-05T03:08:42.03ZS-EPMC128759114166060710.3389/fimmu.2025.1650375