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

Epigenomics. 2015;7(4):539-51. doi: 10.2217/epi.15.15.

Abstract

Aim: Alterations in DNA methylation contribute to the abnormal phenotype of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). We profiled genome-wide DNA methylation in these cells from synovial fluid, a more readily accessible source of disease-associated cells.

Patients & methods: Genome-wide DNA methylation was interrogated in fluid-derived FLS from five RA and six osteoarthritis patients using Human Methylation 450 Bead Chip and bisulfite pyrosequencing.

Results: Array analysis identified 328 CpGs, representing 195 genes, that were differentially methylated between RA and osteoarthritis 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.

Conclusion: Synovial fluid-derived RA FLS show methylation changes common with tissue-derived FLS, supporting the use of fluid-derived FLS for future investigations.

Keywords: DNA methylation; epigenetics; fibroblast-like synoviocyte; osteoarthritis; rheumatoid arthritis; synovial fluid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / genetics*
  • CpG Islands
  • DNA Methylation*
  • Female
  • Genome
  • Humans
  • Male
  • Osteoarthritis / genetics*
  • Synovial Fluid / cytology*
  • Synovial Fluid / metabolism