Modulation of cell function by microRNA in rheumatoid arthritis.

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19605
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Nagasaki University
• Principal Investigator: IWAMOTO Naoki 長崎大学, 医歯薬学総合研究科(医学系), 助教 (80437897)
• Co-Investigator(Renkei-kenkyūsha): KAWAKAMI Atsushi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639) ; TAMAI Mami 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (60380862) ; ICHINOSE Kunihiro 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60437895) ; ARIMA Kazuhiko 長崎大学, 医歯薬学総合研究科(医学系), 講師 (30423635)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 関節リウマチ / microRNA / 骨芽細胞 / 滑膜細胞 / MTX / miR-218 / miR-887

Outline of Final Research Achievements

Fibroblast-like synovial cells from RA patients (RA-FLS) can differentiate into osteoblast and miR-218 was down-regulated during osteogenic differentiation of RA-FLS. Induction of miR-218 in RA-FLS decreased ROBO1 expression. Conversely, the knockdown of miR-218 increased the expression of ROBO1. Finally, miR-218 promoted osteogenic differentiation of RA-FLS through DKK-1 suppression. Our results showed that miR-218 modulate osteogenic differentiation of RA-FLS through ROBO1/DKK-1 axis.
In RA-FLS, miR-887 was upregulated in response to MTX. Overexpression of miR-887 decreased cytokine/chemokine production such as GM-CSF, MIP-1a. Furthermore, overexpression of miR-887 reduced migratory activity in scratch assay. MiR-887 might be downstream effector of MTX in suppression of its cytokine production and invasive phenotype. This knowledge may also be useful for the development of novel therapeutic strategies based on other treatments able to boost the cellular reservoir of miR-877.

Free Research Field

リウマチ・膠原病内科学