DNA methylation profiling of synovial fluid FLS in rheumatoid arthritis reveals changes common with tissue-derived FLS

Glossop, John R.; Haworth, Kim E.; Emes, Richard D.; Nixon, Nicola B.; Packham, Jon C.; Dawes, Peter T.; Fryer, Anthony A.; Mattey, Derek L.; Farrell, William E.

Abstract

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.

Citation

Glossop, J. R., Haworth, K. E., Emes, R. D., Nixon, N. B., Packham, J. C., Dawes, P. T., Fryer, A. A., Mattey, D. L., & Farrell, W. E. (2015). DNA methylation profiling of synovial fluid FLS in rheumatoid arthritis reveals changes common with tissue-derived FLS. Epigenomics, 7(4), https://doi.org/10.2217/epi.15.15

• Journal Article Type: Article
• Publication Date: Jun 1, 2015
• Deposit Date: Dec 18, 2015
• Publicly Available Date: Dec 18, 2015
• Journal: Epigenomics
• Print ISSN: 1750-1911
• Electronic ISSN: 1750-192X
• Publisher: Future Medicine
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 4
• DOI: https://doi.org/10.2217/epi.15.15
• Keywords: Rheumatoid arthritis; DNA Methylation; Fibroblast-like synoviocyte; Synovial fluid; Epigenetics; Osteoarthritis
• Public URL: https://nottingham-repository.worktribe.com/output/750513
• Publisher URL: http://www.futuremedicine.com/doi/10.2217/epi.15.15
• Contract Date: Dec 18, 2015