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.