Drs. Nakasa and Miyaki contributed equally to this work.
Rheumatoid Arthritis Basic Science Studies
Expression of microRNA-146 in rheumatoid arthritis synovial tissue
Article first published online: 25 APR 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 5, pages 1284–1292, May 2008
How to Cite
Nakasa, T., Miyaki, S., Okubo, A., Hashimoto, M., Nishida, K., Ochi, M. and Asahara, H. (2008), Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis & Rheumatism, 58: 1284–1292. doi: 10.1002/art.23429
- Issue published online: 25 APR 2008
- Article first published online: 25 APR 2008
- Manuscript Accepted: 28 JAN 2008
- Manuscript Received: 9 MAY 2007
- NIH. Grant Numbers: AR-50631, AR-47360
- Arthritis Foundation
- Japan Science and Technology Agency SORST Project
- Japanese National Institute of Biomedical Innovation
- Genome Network Project (MEXT)
Several microRNA, which are ∼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).
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 α (TNFα) and interleukin-1β (IL-1β) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT-PCR.
Mature miR-146a and primary miR-146a/b were highly expressed in RA synovial tissue, which also expressed TNFα, 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 TNFα and IL-1β.
This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFα and IL-1β. Further studies are required to elucidate the function of miR-146 in these tissues.