Mechanism of RORα in Promoting Osteoarthritis through p53 Deubiquitination-Mediated Chondrocyte Ferroptosis

While ferroptosis is increasingly implicated in the pathogenesis of osteoarthritis (OA), a comprehensive transcriptomic profile of this process in human chondrocytes is lacking. We compared the gene expression profiles of primary chondrocytes isolated from normal and OA human cartilage using RNA-seq to identify key regulatory genes and pathways. Subsequently, we performed Gene Ontology (GO) enrichment analysis to characterize the functional significance of differentially expressed genes. The majority of variation was found between OA and normal chondrocytes, revealing a distinct ferroptosis-related gene signature in the diseased state. Specifically, key ferroptosis suppressors, including SLC7A11 and GPX4, were downregulated, while promoters such as ACSL4 and FTH1 were upregulated in OA chondrocytes. Functional clustering based on GO terms highlighted the disruption of iron homeostasis and dysregulation of glutathione metabolism as critical pathways in OA progression. Our findings provide a transcriptomic basis for the pathogenic role of ferroptosis in OA, corroborating in vitro and in vivo functional experiments, and this dataset serves as a resource for investigating novel therapeutic targets.