Expression of microRNA-146 in rheumatoid arthritis synovial tissue

Authors

  • Tomoyuki Nakasa,

    1. National Research Institute for Child Health and Development, Tokyo, Japan
    2. Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
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    • Drs. Nakasa and Miyaki contributed equally to this work.

  • Shigeru Miyaki,

    1. National Research Institute for Child Health and Development, Tokyo, Japan
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    • Drs. Nakasa and Miyaki contributed equally to this work.

  • Atsuko Okubo,

    1. National Research Institute for Child Health and Development, Tokyo, Japan
    2. Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
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  • Megumi Hashimoto,

    1. National Research Institute for Child Health and Development, Tokyo, Japan
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  • Keiichiro Nishida,

    1. Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
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  • Mitsuo Ochi,

    1. Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
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  • Hiroshi Asahara

    Corresponding author
    1. National Research Institute for Child Health and Development, Tokyo, Japan
    2. Scripps Research Institute, La Jolla, California
    • Department of Regenerative Biology and Medicine, National Research Institute for Child Health and Development, Research Institute, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan
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Abstract

Objective

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).

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 α (TNFα) and interleukin-1β (IL-1β) 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 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.

Conclusion

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.

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