Study of the role of miRNA in the regulation of osteoclast differentiation in rheunmatoid arthritis joints

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kobe University
• Principal Investigator: Kawano Seiji 神戸大学, 医学部附属病院, 教授 (20351512)
• Co-Investigator(Kenkyū-buntansha): SAEGUSA Jun 神戸大学, 医学部附属病院, 講師 (20514970) ; NAKAMACHI Yuji 神戸大学, 医学部附属病院, その他(臨床検査技師) (80379429)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: マイクロRNA / 破骨細胞 / 関節リウマチ

Outline of Final Research Achievements

MicroRNAs (miRNAs) are small endogenous, noncoding RNAs that act as post-transcriptional regulators. We analyzed the in vivo effect of miRNA-124 (miR-124, the rat analog of human miR-124a) on adjuvant-induced arthritis (AIA) in rats.　We found that miR-124 suppressed AIA in rats, as demonstrated by decreased synoviocyte proliferation, leukocyte infiltration, and cartilage or bone destruction. Osteoclast counts were reduced in AIA rats treated with pre-miR-124, and protein level of NFATc1 was reduced in AIA joints. Luciferase analysis showed that miR-124 directly targeted the 3’-UTR of the rat NFATc1 mRNAs. MiR-124 also directly targeted the 3’-UTR of human NFATc1 mRNA, and suppressed the differentiation of human osteoclasts.Conclusion. We found that miR-124 ameliorated AIA by suppressing critical prerequisites for arthritis development, such as NFATc1. Thus, we concluded that miR-124a is a candidate for therapeutic use for human rheumatoid arthritis.

Free Research Field

リウマチ膠原病学