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Clarification of inhibitory factor for osteogenic differentiation of human bone marrow stromal cells (MSCs) expressed in the MSCs themselves

Research Project

Project/Area Number 26462259
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Sotome Shinichi  東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (20401391)

Co-Investigator(Kenkyū-buntansha) 大川 淳  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30251507)
吉井 俊貴  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (50583754)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords骨髄間葉系細胞 / 骨再生 / 骨形成抑制因子 / ノックアウト / 過剰発現 / 骨髄間葉系幹細胞
Outline of Final Research Achievements

After repeated cell division, not only differentiation capabilities of MSCs decrease but also the cells express inhibitory factor for their own differentiation capabilities. We compared gene expression of P1-MSCs with P5-MSCs and narrowed down the candidates of the inhibitory factors to five genes: SEPINB2, EPHA5, SCN9A, NTF3 and SCIN. We tried to clarify the effects of each gene on osteoblastic differentiation using over expressing cells and knockout cells of each gene. Among the genes, we successfully established SEPINB2 knockout cells using an immortalized human cell-line, and further, we evaluated effects of SERPINB2 on osteogenic differentiation using a conditioned medium harvested from the culture of the knock out cells. The results indicated SEPINB2 had facilitative effects on osteoblastic differentiation of MSCs by BMP-2 and had inhibitory effects on osteogenic differentiation by dexamethasone.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2016 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (2 results)

  • [Journal Article] Dexamethasone Regulates EphA5, a Potential Inhibitory Factor with Osteogenic Capability of Human Bone Marrow Stromal Cells.2016

    • Author(s)
      Yamada T, Yoshii T, Yasuda H, Okawa A, Sotome S.
    • Journal Title

      Stem Cells Int.

      Volume: 2016 Issue: 1 Pages: 1301608-1301608

    • DOI

      10.1155/2016/1301608

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 1.Bone Defect Regeneration by a Combination of a β-Tricalcium Phosphate Scaffold and Bone Marrow Stromal Cells in a Non-Human Primate Model.2016

    • Author(s)
      Masaoka T, Yoshii T, Yuasa M, Yamada T, Taniyama T, Torigoe I, Shinomiya K, Okawa A, Morita S, *Sotome S
    • Journal Title

      Open Biomed Eng J

      Volume: 10 Issue: 1 Pages: 2-11

    • DOI

      10.2174/1874120701610010002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dexamethasone enhances osteogenic differentiation of bone marrow- and muscle-derived stromal cells and augments ectopic bone formation induced by bone morphogenetic protein-2.2015

    • Author(s)
      Yuasa M, Yamada T, Taniyama T, Masaoka T, Xuetao W, Yoshii T, Horie M, Yasuda H, Uemura T, Okawa A, Sotome S
    • Journal Title

      PLoS One

      Volume: 10 ( 2 )

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] デキサメタゾンが骨髄由来間葉系細胞(BMSCs)に与える影響 骨形成抑制因子との関連2016

    • Author(s)
      山田 剛史, 早乙女 進一, 安田 裕亮, 松本 連平, 吉井 俊貴, 大川 淳
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡県、福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 骨髄由来間葉系細胞(BMSCs)の質 骨形成抑制因子候補EphA5が果たす役割2014

    • Author(s)
      山田剛史、早乙女進一、安田裕亮、谷山崇、吉井俊貴、大川淳
    • Organizer
      第29回日本整形外科学会基礎学術集会
    • Place of Presentation
      鹿児島 城山観光ホテル
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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