Candidate methylated genes in osteoarthritis explored by bioinformatics analysis

Abstract

Background: This study aimed to explore potential novel genes correlated with osteoarthritis (OA).

Methods: The gene expression profile of GSE48422 was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included five arthritic cartilage samples and five non-arthritic cartilage samples from five female OA patients. Differentially methylated genes (DMGs) between the two kinds of samples were identified, followed by their functional analysis and protein-protein interaction (PPI) analysis. Furthermore, the Comparative Toxicogenomics Database (CTD) was used to further identify OA-related genes among these DMGs.

Results: In total, 965 hypermethylated genes and 112 hypomethylated genes were identified in the arthritic cartilage samples. The hypermethylated genes (e.g., ADCY4 and ADCY6) were significantly related to the calcium signaling pathway and gonadotropin-releasing hormone signaling pathway, while the hypomethylated genes were implicated in the mammalian target of rapamycin signaling pathway. In the PPI network, several genes had a higher degree, such as ADCY4, ADCY6 and GPR17, and they interacted with each other. Additionally, 565 DMGs were predicted to be associated with OA, and five of them (e.g., COMP and EDIL3) were previously identified as OA markers.

Conclusions: The methylation of genes ADCY4, ADCY6 and GPR17, as well as the gonadotropin-releasing hormone signaling pathway, was newly found to be potentially associated with OA. They may be novel OA markers.

Keywords: Methylation; Osteoarthritis; Pathway; Protein–protein interaction.