Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-18882
Karouzakis, E; Gay, R E; Gay, S; Neidhart, M (2009). Epigenetic control in rheumatoid arthritis synovial fibroblasts. Nature Reviews. Rheumatology, 5(5):266-272.
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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.
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|Item Type:||Journal Article, refereed, further contribution|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||03 Jun 2009 16:28|
|Last Modified:||27 Nov 2013 16:33|
|Publisher:||Nature Publishing Group|
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