RA (rheumatoid arthritis) is an inflammatory disease of synovial joints affecting approximately 1% of the population. One of the main cell types involved in damage to RA joint tissue is the FLSs (fibroblast-like synoviocytes). These have a semi-transformed, auto-aggressive phenotype typified by loss of contact inhibition, reduced apoptosis and the production of matrix-degrading enzymes. The mechanisms involved in the development of this phenotype are unclear; however, increasing evidence implicates alterations in the epigenetic regulation of gene expression. Reduced acetylation of amino acids in the tails of histone proteins is an epigenetic mark associated with transcriptional repression and is controlled by the HDAC (histone deacetylase) enzyme family. To date, evidence has implicated HDACs in the auto-aggressive phenotype of FLSs, and administration of HDAC inhibitors to both animal models of RA and individuals with juvenile arthritis has shown efficacy in attenuating inflammation and tissue damage. This highlights a role for HDACs in disease pathogenesis and, more importantly, that HDACs are potential novel therapeutic targets.
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Conference Article|
May 23 2013
The role of histone deacetylases in rheumatoid arthritis fibroblast-like synoviocytes
Sarah Hawtree;
Sarah Hawtree
1
1Academic Unit of Rheumatology, Department of Infection and Immunity, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, U.K.
1To whom correspondence should be addressed (sarah.hawtree@sheffield.ac.uk).
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Munitta Muthana;
Munitta Muthana
1Academic Unit of Rheumatology, Department of Infection and Immunity, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, U.K.
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Anthony G. Wilson
Anthony G. Wilson
1Academic Unit of Rheumatology, Department of Infection and Immunity, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, U.K.
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Publisher: Portland Press Ltd
Received:
April 15 2013
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem Soc Trans (2013) 41 (3): 783–788.
Article history
Received:
April 15 2013
Citation
Sarah Hawtree, Munitta Muthana, Anthony G. Wilson; The role of histone deacetylases in rheumatoid arthritis fibroblast-like synoviocytes. Biochem Soc Trans 1 June 2013; 41 (3): 783–788. doi: https://doi.org/10.1042/BST20130053
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