Genome-wide expression and methylation profiling reveal candidate genes in osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) is a common degenerative disease of the synovial joints. Although numerous studies have been performed, the aetiology of OA remains unclear. Evidence suggests that DNA methylation plays important roles in OA.

METHODS: Integrated analysis of five gene expression and one methylation profilings in OA was performed to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs), respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were then conducted to reveal the biological functions of DEGs and DMGs. The protein-protein interaction network was finally constructed.

RESULTS: A set of 500 DEGs and 1219 DMGs in OA was found when compared with normal tissues. Function analysis of DEGs and DMGs revealed 3 critical OA-related pathways. A total of 20 DEGs were screened whose expressions showed strongly negative correlations with DNA methylation levels. Among them, 4 up-regulated DEGs (BST2, HDAC4, ITGB2 and VCAM1) may be closely related to the pathogenesis of OA.

CONCLUSIONS: The results of integrated analysis explored 3 OA-related pathways (rheumatoid arthritis, osteoclast differentiation and ECM-receptor interaction) and 4 candidate genes of OA (BST2, HDAC4, ITGB2 and VCAM1) that may be therapeutic targets.