Identification and analysis of immune aging related biomarkers in cartilage and meniscus tissues of osteoarthritis

This study aimed to investigate the relationship between immunosenescence and osteoarthritis (OA) and analyze its potential clinical implications. Thus, we conducted transcriptome sequencing by collecting clinical meniscus (Aging_meniscus:Control_meniscus = 3:7) and cartilage tissues (Aging_cartilage:Control_cartilage = 2:6). Meanwhile, immune-related genes (IRGs) and aging-related genes (ARGs) were included in this research. The differentially expressed genes (DEGs) between Aging_meniscus and Control_meniscus as well as Aging_cartilage and Control_cartilage were analyzed by differential analysis, respectively. Then, differentially expressed IRGs (DEIRGs) were generated by crossing DEG with IRGs. Similarly, differentially expressed ARGs (DEARGs) were achieved by intersecting DEG and ARGs. To obtain genes simultaneously associated with immune and aging in both meniscus and cartilage samples, biomarkers were screened out by crossing share.IRGs and share.ARGs overlapped by DEIRGs1 and DEIRGs2 as well as DEARGs1 and DEARGs2, respectively. In addition, the biomarkers' functions were analyzed by gene set enrichment analysis (GSEA). To detect the regulatory mechanism, a miRNA-mRNA-transcription factors (TFs) regulatory network and a X2K network were constructed. Moreover, disease association analysis and potential small molecule drugs for biomarkers were also performed to further reveal the possible role of biomarkers for OA. Then, 3 biomarkers, namely Insulin-like Growth Factor 1 Receptor (IGF1R), Interleukin 7 receptor (IL7R) and Leptin receptor (LEPR), were selected out through the intersection of 14 share.IRGs and 4 share.ARGs. And they were all enriched in 'ribosome' from both meniscus and cartilage samples, and had complex regulatory networks. In all, the expression of IGF1R was markedly up-regulated in OA (<i>P</i> < 0.05). Eventually, mecasermin could stably bind to IGF1R and simvastatin could stably bind to LEPR. It suggested that mecasermin and simvastatin may exhibit significant clinical potential in treating immunosenescence-related OA.