Abstract:Objective: To explore the key pathogenic genes involved in osteoarthritis (OA) and potential therapeutic drugs for OA by bioinformatics. Methods: The expression profiles of GSE55235, GSE12021 and GSE55457 were downloaded from the gene expression omnibus (GEO) database. The microarray data were integrated to obtain differentially expressed genes (DEGs) by R software. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichments of DEGs were performed by DAVID online analyses. The protein-protein interaction (PPI) was analyzed by using STRING online database and visual editing by Cytoscape software. Finally, small molecule drugs with potential therapeutic OA were analyzed by connectivity map (cMap) database. Results: A total of 67 DEGs were obtained, of which 18 genes were up-regulated and 49 genes were down-regulated. GO analysis showed that the biological process of DEGs focused on cell proliferation, cell adhesion, response to mechanical stimulus, osteoblast differentiation, and the regulation of cellular response to calcium ions. The main cell composition included extracellular space, endoplasmic reticulum membrane and cyclin-dependent protein kinase holoenzyme complex. The molecular functions included protein homodimerization activity, growth factor activity, transcription factor activity, RNA polymeraseⅡcore promoter proximal region sequence-specific binding, protein heterodimerization activity, peroxidase activity, and MAP kinase tyrosine/serine/threonine phosphatase activity. KEGG pathway analysis showed that these DEGs were mainly involved in the osteoclast differentiation, TNF signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, cytokine-cytokine receptor interaction and Jak-STAT signaling pathway. The top 10 hub genes IL-6, JUN, VEGFA, ATF3, DUSP1, MYC, PTGS2, JUNB, CDKN1A and CD44 were identified from the PPI network. Some potential small molecular drugs for the treatment of OA, such as estradiol and leflunomide, were also been screened. Conclusion: The selected key genes may be the diagnostic markers and potential therapeutic targets of OA, and the selected small molecular drugs may be potential therapeutic drugs for OA treatment.
