Expression of microRNA-146 in rheumatoid arthritis synovial tissue.
OBJECTIVE
Several microRNA, which are approximately 22-nucleotide noncoding RNAs, exhibit tissue-specific or developmental stage-specific expression patterns and are associated with human diseases. The objective of this study was to identify the expression pattern of microRNA-146 (miR-146) in synovial tissue from patients with rheumatoid arthritis (RA).


METHODS
The expression of miR-146 in synovial tissue from 5 patients with RA, 5 patients with osteoarthritis (OA), and 1 normal subject was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by in situ hybridization and immunohistochemistry of tissue sections. Induction of miR-146 following stimulation with tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT-PCR.


RESULTS
Mature miR-146a and primary miR-146a/b were highly expressed in RA synovial tissue, which also expressed TNFalpha, but the 2 microRNA were less highly expressed in OA and normal synovial tissue. In situ hybridization showed primary miR-146a expression in cells of the superficial and sublining layers in synovial tissue from RA patients. Cells positive for miR-146a were primarily CD68+ macrophages, but included several CD3+ T cell subsets and CD79a+ B cells. Expression of miR-146a/b was markedly up-regulated in RASFs after stimulation with TNFalpha and IL-1beta.


CONCLUSIONS
This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFalpha and IL-1beta. Further studies are required to elucidate the function of miR-146 in these tissues.
Nakasa
Tomoyuki
T
National Research Institute for Child Health and Development, Tokyo, Japan.
Miyaki
Shigeru
S
Okubo
Atsuko
A
Hashimoto
Megumi
M
Nishida
Keiichiro
K
Ochi
Mitsuo
M
Asahara
Hiroshi
H
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D013583:Synovial Membrane / Q000378:metabolism*
D035683:MicroRNAs