Autophagy-related genes and pathways was associated with osteoarthritis pathogenesis

Abstract

Background: Patients with osteoarthritis have musculoskeletal-related chronic disability, leading to the high pain intensity. Explaining the molecular mechanisms of osteoarthritis is critial for the diagnosis and cure. Therefore, This research aimed to find key candidate genes involved in osteoarthritis pathogenesis. Methods: We identified differentially expressed genes by integrating multiple microarry datasets in cartilage (GSE43923, GSE113825, GSE129147 and GSE169077). Functional enrichment analysis and protein-protein interaction analysis were performed. Results: We identified sixty-six significantly expression genes (56 up-regulated and 10 down-regulated). Through functional enrichment analysis and protein-protein interaction analysis, we found that the biological process of these genes was enriched in focal adhesion, ECM-receptor interaction and PI3K-Akt signaling, which were closely related with autophagy. Moreover, ceRNA network showed that thirty-four DEGs, including ECM-receptor interaction-related genes (COL4A1, COL4A2 and COL1A2, LAMB1 an THBS2), exist competing endogenous regulating network mediated by 7 lncRNAs and 8 miRNAs. Furthermore, differentially expressed autophagy-related genes (CCL2, CDKN1A, CXCR4, DAPK1, DLC1, FAS, HSPA8, MYC and SERPINA1) were remarkably identified to interact with multiple of the common DEGs in ECM-receptor interaction and PI3K-Akt signaling pathway, suggesting that autophagy plays important role in osteoarthritis pathogenesis by regulating ECM-receptor interaction and PI3K-Akt signaling pathway. Conclusions: This multiple transcriptome analysis identifies ECM-receptor interaction and PI3K-Akt signaling pathway related to osteoarthritis pathogenesis by regulating autophagy and participating in ceRNA network.