title: The role of histone deacetylases in rheumatoid arthritis fibroblast-like synoviocytes.
abstract: 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.
authors.affiliation: Academic Unit of Rheumatology, Department of Infection and Immunity, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK. sarah.hawtree@sheffield.ac.uk
authors.forename: Sarah
authors.initials: S
authors.lastname: Hawtree
authors.forename: Munitta
authors.initials: M
authors.lastname: Muthana
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Wilson
mesh_terms: D000107:Acetylation; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation / Q000235:genetics / Q000502:physiology; D044127:Epigenesis, Genetic / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D013583:Synovial Membrane / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D006657:Histones; D006655:Histone Deacetylases