Osteoarthritis (OA) is a type of arthritis that causes joint pain and limited mobility. In recent years, some studies have shown that the pathological process of OA chondrocytes is related to ferroptosis. Our study aims to identify and validate differentially expressed ferroptosis-related genes (DEFRGs) in OA chondrocytes and to investigate the potential molecular mechanisms. RNA-sequencing and microarray datasets were downloaded from Gene Expression Omnibus (GEO) data repository. Differentially expressed genes (DEGs) were screened by four methods: limma-voom, edgeR, DESeq2, and Wilcoxon rank-sum test. Weighted correlation network analysis (WGCNA), protein-protein interactions (PPI), and cytoHubba of Cytoscape were applied to identify hub genes. Clinical OA cartilage specimens were collected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis, western blotting (WB), histological staining, transmission electron microscopy (TEM), and transfection. Sankey diagram was used to visualize the relationships between the expression level of SLC3A2 in the damaged area and clinical factors. Based on bioinformatics analysis, clinical factors, and experiment validation, SLC3A2 was identified as a hub gene. It was down-regulated in OA cartilage compared to normal cartilage (p < 0.05). Functional enrichment analysis revealed that SLC3A2 was associated with ferroptosis-related functions. Spearman correlation analysis showed that the expression level of SLC3A2 in the OA cartilage-damaged area was closely related to BMI, obesity grade, and Kellgren-Lawrence grade. Furthermore, in vitro experiments validated that SLC3A2 inhibited ferroptosis and suppressed cartilage degeneration in OA. In summary, we demonstrated that SLC3A2 inhibited ferroptosis and suppressed cartilage degeneration in OA. These findings provide a new idea for the study of the pathogenesis of OA, thus providing new means for the clinical diagnosis and targeted therapy of OA.

The current study aimed to identify gene signatures during rheumatoid arthritis (RA) and osteoarthritis (OA), and used these to elucidate the underlying modular mechanisms. Using the Gene Expression Omnibus database, the present study obtained the GSE7669 mRNA expression microarray data from RA and OA synovial fibroblasts (n=6 each). The differentially expressed genes (DEGs) in RA synovial samples compared with OA samples were identified using the Linear Models for Microarray Analysis package. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. A protein‑protein interaction network was constructed and the modules were further analyzed using the Molecular Complex Detection plugin of Cytoscape. A total of 181 DEGs were identified by comparing RA and OA synovial samples (96 up‑ and 85 downregulated genes). The significant DEGs in module 1, including collagen, type I, α 1 (COL1A1), COL3A1, COL4A1 and COL11A1, were predominantly enriched in the extracellular matrix (ECM)‑receptor interaction and focal adhesion pathways. Additionally, significant DEGs in module 2, including radical S‑adenosyl methionine domain containing 2 (RSAD2), 2'‑5'‑oligoadenylate synthetase 2 (OAS2), myxovirus (influenza virus) resistance 1 (MX1) and ISG15 ubiquitin‑like modifier (ISG15), were predominantly associated with immune function pathways. In conclusion, the present study indicated that RSAD2, OAS2, MX1 and ISG15 may be notable gene signatures in RA development via regulation of the immune response. COL3A1, COL4A1, COL1A1 and COL11A1 may be important gene signatures in OA development via involvement in the pathways of ECM-receptor interactions and focal adhesions.