PMID- 26152200
OWN - NLM
STAT- MEDLINE
DCOM- 20160706
LR  - 20150916
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 24
IP  - 19
DP  - 2015 Oct 1
TI  - Histone deacetylase 1 regulates tissue destruction in rheumatoid arthritis.
PG  - 5367-77
LID - 10.1093/hmg/ddv258 [doi]
AB  - Emerging evidence implicates epigenetic mechanisms in the pathogenesis of 
      rheumatoid arthritis (RA). In this study, we have investigated the role of 
      histone deacetylase (HDAC) enzymes in RA synovial fibroblasts (RASFs), a key 
      cellular mediator of cartilage and bone destruction and determined effects of 
      HDAC1 inhibition on both RASF phenotype in vitro, and joint inflammation and 
      damage in the collagen-induced arthritis (CIA) model. Expression of HDACs 1-11 
      messenger ribonucleic acid (mRNA) was compared between RASFs and osteoarthritic 
      synovial fibroblast (OASFs) using quantitative polymerase chain reaction. HDAC1 
      expression in RASFs was inhibited using small interfering RNA (siRNA) technology 
      to assess effects on invasiveness, migration, proliferation and apoptosis. 
      Effects of HDAC1 knockdown (KD) on the transcriptome were assessed using gene 
      microarrays. The effects of siRNA-mediated HDAC(KD) on clinical scores, tissue 
      inflammation and damage were assessed on CIA up to 47 days following 
      immunization. Expression of HDAC1 was significantly higher in RASFs than OASFs. 
      HDAC1(KD) resulted in reduced proliferation, invasion and migration in vitro and 
      transcriptome profiling revealed effects on expression of genes regulating 
      proliferation migration and inflammation. Furthermore, inhibition of HDAC1 in CIA 
      resulted in reduced joint swelling, cartilage and bone damage and lower tumor 
      necrosis factor in joint tissue. These results implicate HDAC1 as an important 
      mediator of tissue damage in RA and support the potential therapeutic utility of 
      inhibitors of this enzyme.
CI  - (c) The Author 2015. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Hawtree, Sarah
AU  - Hawtree S
AD  - Department of Infection and Immunity, University of Sheffield, Sheffield S10 2RX, 
      UK and.
FAU - Muthana, Munitta
AU  - Muthana M
AD  - Department of Infection and Immunity, University of Sheffield, Sheffield S10 2RX, 
      UK and.
FAU - Wilkinson, J Mark
AU  - Wilkinson JM
AD  - Academic Unit of Bone Metabolism, University of Sheffield, Sheffield S10 2RX, UK 
      and.
FAU - Akil, Mohammed
AU  - Akil M
AD  - Department of Infection and Immunity, University of Sheffield, Sheffield S10 2RX, 
      UK and.
FAU - Wilson, Anthony G
AU  - Wilson AG
AD  - Department of Infection and Immunity, University of Sheffield, Sheffield S10 2RX, 
      UK and Conway Institute, Belfield Campus, University College Dublin, Dublin 4, 
      Ireland gerry.wilson@ucd.ie.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150707
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - EC 3.5.1.98 (HDAC1 protein, human)
RN  - EC 3.5.1.98 (Hdac1 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Arthritis, Experimental/genetics/*pathology
MH  - Arthritis, Rheumatoid/genetics/*pathology
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Fibroblasts/enzymology/pathology
MH  - Gene Expression Profiling/methods
MH  - Gene Expression Regulation, Enzymologic
MH  - Histone Deacetylase 1/*genetics
MH  - Humans
MH  - Male
MH  - Mice
MH  - Osteoarthritis/genetics/*pathology
MH  - Synovial Membrane/enzymology/pathology
EDAT- 2015/07/15 06:00
MHDA- 2016/07/07 06:00
CRDT- 2015/07/09 06:00
PHST- 2015/04/28 00:00 [received]
PHST- 2015/07/03 00:00 [accepted]
PHST- 2015/07/09 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/07/07 06:00 [medline]
AID - ddv258 [pii]
AID - 10.1093/hmg/ddv258 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2015 Oct 1;24(19):5367-77. doi: 10.1093/hmg/ddv258. Epub 2015 Jul 
      7.