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PMID: 19412193 Published · ppublish English Journal Article Review

Epigenetic control in rheumatoid arthritis synovial fibroblasts.

Nature reviews. Rheumatology ·Vol. 5 ·No. 5 ·2009-05-00 ·Pages 266-72

Karouzakis E, Gay RE, Gay S, Neidhart M

Abstract

Rheumatoid arthritis synovial fibroblasts (RASFs) are the effector cells of cartilage and bone destruction. These cells show an 'intrinsically' activated and aggressive phenotype that results in the increased production of matrix-degrading enzymes and adhesion molecules, and is conserved over long-term passage in vitro. The three main mechanisms of epigenetic control -- DNA methylation, histone modifications and microRNA activity -- interact in the development of the RASF phenotype. The extent of global DNA methylation is reduced in synoviocytes in situ and RASFs in vitro. In addition, histone hyperacetylation occurs and specific microRNAs are expressed in RASFs. Normal synovial fibroblasts cultured in a hypomethylating milieu acquire an activated phenotype similar to that of RASFs. These findings suggest that epigenetic control, in particular the control of DNA methylation, is deficient in RASFs. Genome-wide analyses of the epigenome will enable the detection of additional genes involved in the pathogenesis of rheumatoid arthritis, the identification of epigenetic biomarkers, and potentially the development of a therapeutic regimen that targets activated RASFs.

MeSH Terms
Arthritis, Rheumatoid/genetics,metabolism,physiopathology Cells, Cultured DNA Methylation Epigenesis, Genetic Fibroblasts/metabolism,pathology Histones/genetics,metabolism Humans MicroRNAs/genetics,metabolism Synovial Membrane/metabolism,pathology,physiopathology Up-Regulation
Chemicals
Histones MicroRNAs
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Karouzakis Emmanuel
Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
Gay Renate E
Gay Steffen
Neidhart Michel
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Article Info
Journal
Nature reviews. Rheumatology
Abbr.
Nat Rev Rheumatol
ISSN
1759-4804
DOI
10.1038/nrrheum.2009.55
Published
2009-05-00
Pages
266-72
Language
English
Region
United States
NLM ID
101500080
Subset
IM
External Links
PubMed source DOI: 10.1038/nrrheum.2009.55 View journal details
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