Comprehensive Analysis of Hub Telomere-Related Genes and Synovial Immune Characteristics in Osteoarthritis

Osteoarthritis (OA) is a degenerative arthritis associated with aging. It is recognized that telomere attrition is a hallmark of aging. However, the transcriptional dynamics of synovial telomere-related genes (TRGs) in OA has not yet been elucidated. OA synovium microarray profiles were sourced from GEO and TRGs from TelNet. GO, KEGG, DO and GSVA enrichment analyses were employed to explore the underlying mechanisms. WGCNA and machine learning methods were utilized to screen hub differentially expressed TRGs (TRDEGs) that highly correlated with OA traits (hub OA-TRDEGs). Nomograms and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of hub OA-TRDEGs. An RNA-binding protein (RBP) network was developed to predict potential RBP target genes.​ The CIBERSORT analysis was performed to assess associations between hub OA-TRDEGs and immune infiltration. We identified 77 TRDEGs in normal and OA synovium samples. Functional enrichment analysis implicated these ge-nes primarily in metabolism regulation, DNA repair and inflammatory response. LTA4H, HNMT, ANKMY2, UFSP2, HLTF and RPA3 were established as hub OA-TRDEGs, demonstrating strong diagnostic performance for OA. Wilcox testing confirmed significant up-regulation of all hub OA-TRDEGs in OA synovium - a finding validated through independent datasets and qRT-PCR assays. Immune infiltration analysis further indicated that ​​resting mast cells, CD4+ memory resting T cells and activated mast cells are implicated in OA pathogenesis and exhibit significant correlations with hub OA-TRDEGs. These results nominate hub OA-TRDEGs as potential dia-gnostic biomarkers and underscore immune cell infiltration as a critical driver of OA progression.