Genome-wide DNA methylation study identifies significant epigenomic changes in osteoarthritic cartilage.

摘要: Objective To perform a genome-wide DNA methylation study to identify changes in osteoarthritic (OA) cartilage tissue. Methods The contribution of differentially methylated genes OA pathogenesis was assessed by bioinformatic analysis, gene expression and histopathologic severity correlation. Genome-wide profiling >485,000 sites performed on eroded intact from within the same joint 24 patients undergoing hip arthroplasty for OA. Genes with CpG were analyzed overrepresented ontologies, pathways, upstream regulators. The messenger RNA subset reverse transcription–polymerase chain reaction. Histopathology graded modified Mankin score correlated methylation. Results We identified 550 Most (69%) hypomethylated enriched among enhancers. We found differential prior links OA, including RUNX1, RUNX2, DLX5, FURIN, HTRA1, FGFR2, NFATC1, SNCAIP, COL11A2. Among these, COL11A2 also expressed. Furthermore, we approximately one-third known susceptibility genes. genes, regulator analysis showed enrichment TGFB1 (P = 4.40 × 10−5) several microRNAs miR-128 4.48 10−13), miR-27a 4.15 10−12), miR-9 9.20 10−10). Finally, strong correlations between 20 histologic OA. Conclusion Our data implicate epigenetic dysregulation host pathways number