Candidate methylated genes in osteoarthritis explored by bioinformatics analysis.
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.
Shaanxi University of Chinese Medicine, Shiji Avenue, Xi'an-Xianyang New Economic Zone, Shaanxi 712046, PR China.
Jie
J
Liu
Department of Osteonecrosis and Joint Reconstruction, Honghui Hospital, Xi'an Jiao Tong University Health Science Center, 555 Youyi East Road, Xi'an, Shaanxi 710068, PR China. Electronic address: haoyangqh@163.com.
Yangquan
Y
Hao
Shaanxi University of Chinese Medicine, Shiji Avenue, Xi'an-Xianyang New Economic Zone, Shaanxi 712046, PR China.
Yugui
Y
Wang
Department of Osteonecrosis and Joint Reconstruction, Honghui Hospital, Xi'an Jiao Tong University Health Science Center, 555 Youyi East Road, Xi'an, Shaanxi 710068, PR China.
Shouye
S
Hu
Department of Osteonecrosis and Joint Reconstruction, Honghui Hospital, Xi'an Jiao Tong University Health Science Center, 555 Youyi East Road, Xi'an, Shaanxi 710068, PR China.
Ke
K
Xu
Department of Osteonecrosis and Joint Reconstruction, Honghui Hospital, Xi'an Jiao Tong University Health Science Center, 555 Youyi East Road, Xi'an, Shaanxi 710068, PR China.
Chao
C
Lu
D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D006801:Humans; D010003:Osteoarthritis / Q000235:genetics*; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D059467:Transcriptome
Methylation; Osteoarthritis; Pathway; Protein–protein interaction