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DNA methylation associated with cartilage changes in osteoarthritis
DOI:10.1038/bonekey.2015.14
Jeffries et al. studied samples of intact and damaged cartilage from 24 patients with osteoarthritis (OA) undergoing hip arthroplasty. The samples were subjected to genome-wide DNA methylation profiling at over 485,000 methylation sites.
The results revealed a total of 550 differentially methylated sites; 69% were hypomethylated while the rest were hypermethylated. A third of all genes previously associated with OA were differentially methylated, including, RUNX2, DLX5, FURIN, NFATC1, SNCAIP, HTRA1, RUNX1, FGFR2 and COL11A2. The four latter genes were also expressed differentially when the eroded and intact cartilage samples were compared.
A subset of samples was assessed using modified Mankin scoring to grade the level of disease activity present. The number of altered methylation correlated significantly with higher disease activity scores; 17 were negatively correlated with a higher grade (more severe histologic damage) while 3 were positively correlated. The authors suggest that this could help in the search for biomarkers of OA activity.
Editor’s comment: In addition to demonstrating differential methylation expression in a subset of OA susceptibility genes, this study also identified correlations between CpG methylation sites and histopathology (histologic severity scores).
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