PMID- 18383392
OWN - NLM
STAT- MEDLINE
DCOM- 20080521
LR  - 20220408
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 58
IP  - 4
DP  - 2008 Apr
TI  - Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in 
      rheumatoid arthritis.
PG  - 1001-9
LID - 10.1002/art.23386 [doi]
AB  - OBJECTIVE: MicroRNAs (miRNA) have recently emerged as a new class of modulators 
      of gene expression. In this study we investigated the expression, regulation, and 
      function of miR-155 and miR-146a in rheumatoid arthritis (RA) synovial 
      fibroblasts (RASFs) and RA synovial tissue. METHODS: Locked nucleic acid 
      microarray was used to screen for differentially expressed miRNA in RASFs treated 
      with tumor necrosis factor alpha (TNFalpha). TaqMan-based real-time polymerase 
      chain reaction was applied to measure the levels of miR-155 and miR-146a. 
      Enforced overexpression of miR-155 was used to investigate the function of 
      miR-155 in RASFs. RESULTS: Microarray analysis of miRNA expressed in RASFs 
      treated with TNFalpha revealed a prominent up-regulation of miR-155. Constitutive 
      expression of both miR-155 and miR-146a was higher in RASFs than in those from 
      patients with osteoarthritis (OA), and expression of miR-155 could be further 
      induced by TNFalpha, interleukin-1beta, lipopolysaccharide, poly(I-C), and 
      bacterial lipoprotein. The expression of miR-155 in RA synovial tissue was higher 
      than in OA synovial tissue. Enforced expression of miR-155 in RASFs was found to 
      repress the levels of matrix metalloproteinase 3 (MMP-3) and reduce the induction 
      of MMPs 3 and 1 by Toll-like receptor ligands and cytokines. Moreover, compared 
      with monocytes from RA peripheral blood, RA synovial fluid monocytes displayed 
      higher levels of miR-155. CONCLUSION: This study provides the first description 
      of increased expression of miRNA miR-155 and miR-146a in RA. Based on these 
      findings, we postulate that the inflammatory milieu may alter miRNA expression 
      profiles in resident cells of the rheumatoid joints. Considering the repressive 
      effect of miR-155 on the expression of MMPs 3 and 1 in RASFs, we hypothesize that 
      miR-155 may be involved in modulation of the destructive properties of RASFs.
FAU - Stanczyk, Joanna
AU  - Stanczyk J
AD  - Center of Experimental Rheumatology, University Hospital Zurich, and Zurich 
      Center of Integrative Human Physiology, University of Zurich, Zurich, 
      Switzerland. joanna.stanczyk@usz.ch
FAU - Pedrioli, Deena M Leslie
AU  - Pedrioli DM
FAU - Brentano, Fabia
AU  - Brentano F
FAU - Sanchez-Pernaute, Olga
AU  - Sanchez-Pernaute O
FAU - Kolling, Christoph
AU  - Kolling C
FAU - Gay, Renate E
AU  - Gay RE
FAU - Detmar, Michael
AU  - Detmar M
FAU - Gay, Steffen
AU  - Gay S
FAU - Kyburz, Diego
AU  - Kyburz D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (MIRN146 microRNA, human)
RN  - 0 (MIRN155 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Arthritis, Rheumatoid/*metabolism/physiopathology
MH  - Cohort Studies
MH  - Fibroblasts/*metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 3/immunology/metabolism
MH  - MicroRNAs/immunology/*metabolism
MH  - Monocytes/immunology/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Synovial Fluid/cytology/immunology
MH  - Synovial Membrane/metabolism/*physiopathology
EDAT- 2008/04/03 09:00
MHDA- 2008/05/22 09:00
CRDT- 2008/04/03 09:00
PHST- 2008/04/03 09:00 [pubmed]
PHST- 2008/05/22 09:00 [medline]
PHST- 2008/04/03 09:00 [entrez]
AID - 10.1002/art.23386 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2008 Apr;58(4):1001-9. doi: 10.1002/art.23386.