Expression of MicroRNA-146 in rheumatoid arthritis synovial tissue

Objective. Several microRNA, which are similar to 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 (TNF alpha) and interleukin-1 beta (IL-1 beta) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT-PCR. Results. Mature miR-146a and primary miR146a/b were highly expressed in RA synovial tissue, which also expressed TNF alpha, 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 upregulated in RASFs after stimulation with TNF alpha and IL-1 beta. Conclusion. This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNF alpha and IL-1 beta. Further studies are required to elucidate the function of miR-146 in these tissues.