Analysis of methylation datasets identified significantly changed genes and functional pathways in osteoarthritis

Researches indicate that epigenetics was involved in osteoarthritis (OA). The purpose of this study was to describe the alterations of DNA methylation in hip and knee OA by comparing DNA methylome of OA cartilage and non-OA samples and to identify novel genes and pathways associated with OA.

We gained two expression profiling datasets (GSE73626 and GSE63695) from the GEO dataset. The RnBeads in R package was used to identify differentially methylated CpG sites. Genes that showed significant differences in DNA methylation between OA and normal control groups underwent functional annotation analysis using the online tool of GeneCodis. Furthermore, we used the Sequenom MassARRAY platform (CapitalBio, Beijing, China) to perform the quantitative methylation analysis.

A total of 249 hypermethylated sites and 96 hypomethylated sites were obtained from OA samples compared with normal control samples. Functional analysis of differentially methylated genes obtained that embryonic skeletal system morphogenesis, cartilage development, and skeletal system development may be involved in the pathogenesis of OA. Eight genes including HOXB3, HOXB4, HOXB6, HOXC4, HOXC10, HOXD3, TBX3, and TBX5 were identified as potential novel biomarkers for OA.

Taken together, our study found different molecular characteristics between OA patients and normal controls. This may provide new clues to elucidate the pathogenesis of OA.Key Points• Embryonic skeletal system morphogenesis, cartilage development, skeletal system development may be involved in the pathogenesis of OA.• Eight genes are identified as potential novel markers for OA.• Our future in vivo molecular intervention experiments will extend our current findings.