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Establishment of novel therapy for intractable necrosis of the jaw with mesenchymal stem cells-induced anti-inflammatory macrophages

Research Project

Project/Area Number 17K19774
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Oral Science and related fields
Research InstitutionIwate Medical University

Principal Investigator

ISHISAKI Akira  岩手医科大学, 歯学部, 教授 (20356439)

Co-Investigator(Kenkyū-buntansha) 藤原 尚樹  岩手医科大学, 歯学部, 准教授 (20190100)
帖佐 直幸  岩手医科大学, 歯学部, 准教授 (80326694)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsビスホスホネート / BRONJ / 間葉系幹細胞 / 歯学
Outline of Final Research Achievements

We tried to establish research basis for novel therapy against BRONJ with mesenchymal stem cells (MSCs)-induced anti-inflammatory macrophages.
We found that expression level of IL-10 was up-regulated in bone marrow-derived lineage-positive (Lin (+)) blood cells co-cultured with MSCs. We also found that MSCs-derived liquid factor and cell-cell adhesion between MSCs and Lin (+) blood cells synergistically increased IL-10 expression in the Lin (+) blood cells. We keep developing our research results into the establishment of novel therapy against for BRONJ.

Academic Significance and Societal Importance of the Research Achievements

ビスホスホネートbisphosphonate (BP)は、悪性腫瘍の形成に伴う高カルシウム血症、腫瘍の骨転移、ならびに骨粗鬆症において、破骨細胞の骨吸収を抑制することによりそれらの症状を改善する臨床的に有効性の高い薬剤である。しかし、近年、BP系薬剤関連顎骨壊死(bisphosphonate-related osteonecrosis of the jaw (BRONJ)が高い頻度で発生している。今回の我々の研究成果により、BRONJの新規治療戦略確立のための基盤が確立された。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (5 results)

  • [Journal Article] Insulin-like growth factor-I stimulates the disintegration of Hertwig’s epithelial root sheath and cellular cementogenesis in mouse molars in vitro.2019

    • Author(s)
      Naoki Fujiwara and Akira Fujimura
    • Journal Title

      Dental Journal of Iwate Medical University

      Volume: 43 Pages: 140-152

    • NAID

      130007893392

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell?cell interactions between monocytes/macrophages and synoviocyte-like cells promote inflammatory cell infiltration mediated by augmentation of MCP-1 production in temporomandibular joint2018

    • Author(s)
      Ibi Miho、Horie Sawa、Kyakumoto Seiko、Chosa Naoyuki、Yoshida Mariko、Kamo Masaharu、Ohtsuka Masato、Ishisaki Akira
    • Journal Title

      Bioscience Reports

      Volume: 38 Issue: 2 Pages: 20171217-20171217

    • DOI

      10.1042/bsr20171217

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 間葉系幹細胞を利用した再生医療における新たな戦略2018

    • Author(s)
      石崎明, 客本齊子,横田聖司,加茂政晴,帖佐直幸
    • Journal Title

      お茶の水醫學雑誌

      Volume: 66 Pages: 247-258

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Harmine promotes molar root development via SMAD1/5/8 phosphorylation.2018

    • Author(s)
      Fujiwara N, Lee JW, Kumakami-Sakano M, Otsu K, Woo JT, Iseki S, Ota
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 497 Issue: 3 Pages: 924-929

    • DOI

      10.1016/j.bbrc.2017.12.062

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SCRG1 suppresses LPS-induced CCL22 production through ERK1/2 activation in mouse macrophage Raw264.7 cells.2017

    • Author(s)
      Inoue M., Yamada J, Aomatsu-Kikuchi E., Satoh K., Kondo H., Ishisaki A., Chosa N.
    • Journal Title

      Molecular Medicine Reports, in press.

      Volume: 1 Issue: 6 Pages: 1-8

    • DOI

      10.3892/mmr.2017.6492

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] α2-antiplasmin modulates bone formation by negatively regulating osteoblast differentiation and function2017

    • Author(s)
      Kanno Yosuke、Ishisaki Akira、Kuretake Hiromi、Maruyama Chihiro、Matsuda Ayaka、Matsuo Osamu
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 40 Issue: 3 Pages: 854-858

    • DOI

      10.3892/ijmm.2017.3055

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 顎関節由来線維芽細胞様滑膜細胞におけるプリン体作動性シグナルの役割2018

    • Author(s)
      横田聖司、帖佐直幸、松本識野、客本齊子、加茂政晴、佐藤和朗、石崎 明
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞外ヌクレオチドが顎関節由来線維芽細胞様滑膜細胞に与える影響について2018

    • Author(s)
      松本識野、横田聖司、帖佐直幸、菊池恵美子、木村仁迪、加茂政晴、佐藤和朗、石崎 明
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 歯周靭帯由来細胞における神経栄養因子NGFの発現機構に関する研究2017

    • Author(s)
      太田 麻衣子、帖佐 直幸、横田 聖司、客本 齊子、加茂 政晴、佐藤 健一、城 茂治、石崎 明
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 歯科材料からの溶出成分がヒト間葉系幹細胞の骨芽細胞分化に与える影響2017

    • Author(s)
      根本 章、帖佐 直幸、客本 齊子、横田 聖司、加茂 政晴、野田  守、石崎  明
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Hertwig上皮鞘から遊走する細胞動態の解析2017

    • Author(s)
      藤原尚樹、大津圭史、原田英光
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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