Comprehensive Analysis of Hub Genes and Core Pathways Associated with Osteoarthritis Based on Bioinformatics

Abstract

Background: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by inflammation, articular cartilage degradation, joint discomfort, and limited function. So far, there is a lack of effective treatments for OA. This study aimed to investigate the function of hub genes and the potential mechanisms of regulation. Methods: The whole data of microarray datasets, consist of 12 control groups of OA patients’ chondrocyte and 12 groups of OA patients’ chondrocyte with COT from GSE75181. Differentially expressed genes (DEGs), Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed. Protein-Protein Interaction (PPI) network and Gene Set Enrichment Analysis (GSEA) were performed. Cytoscape was used to identify central genes. Finally, the CCK-8 cell proliferation assay was used to verify the role of the gene HSPA4 in OA by down-regulating the expression of HSPA4. Result: A total of 274 up-regulated and 164 down-regulated genes were identified in this study, 438 DEGs were related to OA patients treated with COT mixture in the dataset. DEGs in OA patients treated with COT mixture was enriched in unfolded protein, MAPK signaling pathway and Extracellular matrix organization. GSEA indicated that Dorsal spinal cord development, Regulation of presynaptic cytosolic calcium ion concentration, sinus bradycardia and prolonged qtc interval were related to the tumorigenesis of OA patients treated with COT mixture. Finally, 6 hub genes (HSPA4, MYC, HSPA8, COL1A1, COL3A1 and CTGF) were determined through the Cytoscape plugin. The CCK-8 cell proliferation assay showed that HSPA4 gene knockdown could inhibit the proliferation of VSMC. Conclusions: Our study results suggest a potential mechanism by which HSPA4 affects the occurrence and progression of OA. The results may help the understanding on the biological system of OA patients treated with COT cocktails and on the development of novel treatments for OA.