Modulation of cell function by microRNA in rheumatoid arthritis.

• 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
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 関節リウマチ / microRNA / 骨芽細胞 / 滑膜細胞 / MTX / miR-218 / miR-887 / トファシチニブ / GM-CSF / 滑膜線維芽細胞

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.

Research Products

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  • Journal Title: Frontiers in Immunology Volume: 8 Pages: 1958-1958
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• [Journal Article] Novel anti-suprabasin antibodies may contribute to the pathogenesis of neuropsychiatric systemic lupus erythematosus. (2018)
  • Author(s): Ichinose K, Ohyama K, Furukawa K, Higuchi O, Mukaino A, Satoh K, Nakane S, Shimizu T, Umeda M, Fukui S, Nishino A, Nakajima H, Koga T, Kawashiri SY, Iwamoto N, Tamai M, Nakamura H, Origuchi T, Yoshida M, Kuroda N, Kawakami A.
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• [Journal Article] CD4+ CD52lo T-cell expression contributes to the development of systemic lupus erythematosus. (2018)
  • Author(s): Umeda M, Koga T, Ichinose K(corresponding author), Igawa T, Sato T, Takatani A, Shimizu T, Fukui S, Nishino A, Horai Y, Hirai Y, Kawashiri SY, Iwamoto N, Aramaki T, Tamai M, Nakamura H, Yamamoto K, Abiru N, Origuchi T, Ueki Y, Kawakami A.
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• [Journal Article] MicroRNA-204-3p inhibits lipopolysaccharide-induced cytokines in familial Mediterranean fever via the phosphoinositide 3-kinase γ pathway (2017)
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• [Journal Article] Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis (2017)
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  • Journal Title: PLoS One Volume: 12 Issue: 5 Pages: 0177057-0177057
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  • NAID: 120006987500
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• [Journal Article] Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled (2017)
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  • Journal Title: Arthritis Research & Therapy Volume: 19 Issue: 1 Pages: 108-108
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• [Journal Article] HR-pQCTがもたらす関節リウマチ骨破壊新知見 (2017)
  • Author(s): 岩本直樹、千葉恒、川上純
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• [Journal Article] Baseline MRI bone erosion predicts the subsequent radiographic progression in early rheumatoid arthritis patients who achieved sustained good clinical response. (2017)
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  • Journal Title: Mod Rheumatol. Volume: Mar 8 Pages: 1-6
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• [Journal Article] Synovitis of sternoclavicular and peripheral joints can be detected by ultrasound in patients with SAPHO syndrome. (2016)
  • Author(s): Umeda M, Kawashiri SY, Nishino A, Koga T, Ichinose K, Michitsuji T, Shimizu T, Fukui S, Nakashima Y, Hirai Y, Iwamoto N, Aramaki T, Tamai M, Nakamura H, Origuchi T, Ueki Y, Kawakami A.
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• [Journal Article] Assessment of both articular synovitis and tenosynovitis by ultrasound is useful for evaluations of hand dysfunction in early rheumatoid arthritis p (2016)
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  • Journal Title: Mod Rheumatol. Volume: Nov 15 Pages: 1-4
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• [Journal Article] Rapid improvement of Clinical Disease Activity Index (CDAI) at 3 months predicts a preferable CDAI outcome at 1 year in active rheumatoid arthritis patients treated with tocilizumab: results from an observational investigation of daily clinical practice. (2016)
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  • Journal Title: Clin Exp Rheumatol. Volume: 34 Pages: 808-812
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• [Journal Article] MRI bone oedema at enrollment predicts rapid radiographic progression over 1 year in early rheumatoid arthritis patients: results from the Nagasaki University Early Arthritis Cohort (2016)
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  • DOI: 10.3899/jrheum.150988
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• [Journal Article] Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice: A Japanese Multicenter, Prospective Longitudinal Cohort Study for Achieving a Treat-to-Target Strategy. (2016)
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• [Journal Article] Bioanalysis of bevacizumab and infliximab by high-temperature reversed-phase liquid chromatography with fluorescence detection after immunoaffinity magnetic purification (2016)
  • Author(s): K. Todoroki, T. Nakano, Y. Eda, K. Ohyama, H. Hayashi , D. Tsuji, J.Z. Min, K. Inoue, N. Iwamoto, A. Kawakami, Y. Ueki, K. Itoh, T. Toyo'oka
  • Journal Title: Anal. Chim. Acta Volume: 916 Pages: 112-119
  • DOI: 10.1016/j.aca.2016.02.029
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 関節リウマチにおけるthrombospondin-1の意義 (2016)
  • Author(s): 岩本 直樹, 鈴木 貴久、大山 要、黒田 直敬、川上純.
  • Journal Title: リウマチ科 Volume: 56 Pages: 193-196
• [Journal Article] 関節リウマチ薬物治療の最新知見 “アバタセプト” (2016)
  • Author(s): 岩本 直樹, 川上純.
  • Journal Title: 日本臨床 Volume: 6 Pages: 968-973
• [Presentation] 関節リウマチ患者におけるトファシチニブの有効性および安全性の検討 -市販後新規開始例の検討- （第2報） (2017)
  • Author(s): 岩本直樹
  • Organizer: 第61回日本リウマチ学会
• [Presentation] MicroRNAによる関節リウマチ滑膜線維芽細胞の骨芽細胞分化誘導の検討 (2017)
  • Author(s): 岩本直樹
  • Organizer: 第38会日本炎症再生学会
• [Presentation] ステロイド性骨粗鬆症におけるビスホスホネート、テリパラチドからデノスマブへの切り替え療法の有用性の検討 (2017)
  • Author(s): 岩本直樹
  • Organizer: 第19回日本骨粗鬆症学会
• [Presentation] MICRORNA PROFILING OF MTX-TREATED FIBROBLAST-LIKE SYNOVIAL CELLS IN RHEUMATOID ARTHRITIS REVEALED A POSSIBILITY OF MICRORNA-887-3P AS NOVEL THERAPEUTIC TARGET OF RA (2017)
  • Author(s): 岩本直樹
  • Organizer: 2017欧州リウマチ学会
  • Int'l Joint Research
• [Presentation] ステロイド性骨粗鬆症におけるビスホスホネート、テリパラチドからデノスマブへの切り替え療法の有用性の検討 (2016)
  • Author(s): 岩本直樹
  • Organizer: 第31回日本臨床リウマチ学会
  • Place of Presentation: 京王プラザホテル（東京都、新宿区）
  • Year and Date: 2016-10-29
• [Presentation] 自己免疫疾患とmicroRNA (2016)
  • Author(s): 岩本直樹
  • Organizer: 第3回JCRベーシックリサーチカンファレンス
  • Place of Presentation: アキバプラザ（東京都、千代田区）
  • Year and Date: 2016-10-14
  • Invited
• [Presentation] Osteogenic differentiation of fibroblast-like synovial cells in Rheumatotid arthritis is induced by microRNA-218 through ROBO/Slit pathway (2016)
  • Author(s): 岩本直樹
  • Organizer: 2016アジア太平洋リウマチ学会
  • Place of Presentation: 上海(中国）
  • Year and Date: 2016-09-26
• [Presentation] 関節リウマチにおける実臨床でのトファシチニブの作用および免疫制御のpros and cons (2016)
  • Author(s): 岩本直樹
  • Organizer: 2016年臨床免疫学会
  • Place of Presentation: 京王プラザホテル（東京都、新宿区）
  • Year and Date: 2016-09-08
  • Invited
• [Presentation] Osteogenic differentiation of fibroblast-like synovial cells in Rheumatotid arthritis is induced by microRNA-218 through ROBO/Slit pathway (2016)
  • Author(s): 岩本直樹
  • Organizer: 第60回日本リウマチ学会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2016-04-21
• [Presentation] 関節リウマチにおけるトファシチニブの有効性および安全性の検討 (2016)
  • Author(s): 岩本直樹
  • Organizer: 第60回日本リウマチ学会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2016-04-21