| Summary: | Aims: Alterations in DNA methylation contribute to the abnormal phenotype of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Herein, we performed genome-wide DNA methylation profiling of RA FLS derived from synovial fluid, a more readily accessible source of disease-associated cells.
Patients & Methods: Synovial fluid-derived FLS were isolated and expanded in vitro from 12 patients with RA and osteoarthritis (OA). DNA methylation was interrogated using HumanMethylation450 BeadChips and bisulfite pyrosequencing.
Results: Array analysis identified 328 CpGs, representing 195 genes, that were differentially methylated between RA and OA fluid-derived FLS. Comparison with the genes identified in two independent studies of tissue-derived FLS revealed 73 genes in common (~40%), of which 22 shared identity with both studies. Pyrosequencing confirmed altered methylation of these genes.
Conclusions: Synovial fluid-derived RA FLS show methylation changes across multiple genes. A subset of these are common with tissue-derived FLS, supporting the use of fluid-derived FLS for future investigations.
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