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Mechanisms involved in regulation of osteoclastogenesis by glucan through autophagy

Research Project

Project/Area Number 18K09797
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionKyushu Dental College

Principal Investigator

Ariyoshi Wataru  九州歯科大学, 歯学部, 教授 (40405551)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords破骨細胞 / β-glucan / dectin-1 / オートファジー / ユビキチン/プロテアソームシステム / spleen tyrosine kinas / nuclear factor-kappa B / Irf-8 / 炎症性骨破壊 / spleen tyrosine kinase / エンドサイトーシス / 小胞体ストレス応答 / 破骨細胞細胞 / 炎症性骨吸収
Outline of Final Research Achievements

In this study, we evaluated the bioactivity of several β‐glucans on receptor activator of nuclear factor‐kappa B ligand (RANKL)‐induced osteoclastogenesis and observed that some β‐glucan inhibited this process in mouse bone marrow cells and dectin‐1-overexpressing RAW264.7 cells.
β-glucan binds to dectin‐1 expressed on osteoclast precursors and attenuates RANKL‐induced osteoclast differentiation by down-regulating nuclear factor of activated T cell c1 (NFATc1) activation. Moreover, we found that the inhibition of NFATc1 activation by β-glucan is dependent on the (1) suppression of NF‐κB cascade, (2) stimulation of interferon regulatory factor 8 (Irf‐8), negative regulators of osteoclastogenesis by up-regulating their transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp 1), and (3) down-regulation of the Spleen tyrosine kinase (Syk)‐mediated signaling by degrading Syk protein via autophagy and the ubiquitin/proteasome system.

Academic Significance and Societal Importance of the Research Achievements

破骨細胞前駆細胞上に特異的に発現するβ-glucan認識受容体であるdectin-1に注目し、研究を展開した結果、dectin-1受容体に結合したβ-glucanが、オートファジーなどを介して破骨細胞分化を抑制することを見出した。このことから、β-glucanは、将来的に臨床応用可能な、選択性の高い骨代謝治療薬の開発に極めて有効であると考える。さらに、当該研究で得られた知見は、骨代謝疾患に対する新たな治療戦略確立に向けての展開にとどまらず、骨代謝制御機構の免疫学的アプローチによる解析を通じて、数多く存在する骨と免疫系とが関わる疾患の病態生理の解明にも寄与するものと期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (23 results)

All 2021 2020 2019 2018 Other

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Schizophyllum commune β-glucan: Effect on interleukin-10 expression induced by lipopolysaccharide from periodontopathic bacteria.2021

    • Author(s)
      Chuencheewit Thongsiri, Yoshie Nagai-Yoshioka, Ryota Yamasaki, Yoshiyuki Adachi, Michihiko Usui, Keisuke Nakashima, Tatsuji Nishihara, Wataru Ariyoshi
    • Journal Title

      Carbohydrate polymers

      Volume: 253 Pages: 117285-117285

    • DOI

      10.1016/j.carbpol.2020.117285

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dectin-1-mediated suppression of RANKL-induced osteoclastogenesis by glucan from baker's yeast2021

    • Author(s)
      Shiika Hara, Yoshie Nagai-Yoshioka, Ryota Yamasaki, Yoshiyuki Adachi, Yuko Fujita, Kouji Watanabe, Kenshi Maki, Tatsuji Nishihara, Wataru Ariyoshi
    • Journal Title

      J Cell Physiol

      Volume: 236 Issue: 7 Pages: 5098-5107

    • DOI

      10.1002/jcp.30217

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biological Effects of β-Glucans on Osteoclastogenesis2021

    • Author(s)
      Ariyoshi Wataru、Hara Shiika、Koga Ayaka、Nagai-Yoshioka Yoshie、Yamasaki Ryota
    • Journal Title

      Molecules

      Volume: 26 Issue: 7 Pages: 1982-1982

    • DOI

      10.3390/molecules26071982

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 3D spheroid culture models for chondrocytes using polyethylene glycol-coated microfabricated chip.2020

    • Author(s)
      Wataru Ariyoshi, Michihiko Usui, Kotaro Sano, Aki Kawano, Toshinori Okinaga, Keisuke Nakashima, Kohji Nakazawa, Tatsuji Nishihara
    • Journal Title

      Biomedical research (Tokyo, Japan)

      Volume: 41 Issue: 4 Pages: 187-197

    • DOI

      10.2220/biomedres.41.187

    • NAID

      130007887499

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] β-glucan suppresses cell death of ASC deficient macrophages invaded by periodontopathic bacteria through the caspase-11 pathway2019

    • Author(s)
      Inoue Maki、Okinaga Toshinori、Usui Michihiko、Kawano Aki、Thongsiri Chuencheewit、Nakashima Keisuke、Ariyoshi Wataru、Nishihara Tatsuji
    • Journal Title

      FEMS Microbiology Letters

      Volume: 366 Issue: 8

    • DOI

      10.1093/femsle/fnz093

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Biological Effects of Interleukin-17A on Adhesion Molecules Expression and Foam Cell Formation in Atherosclerotic Lesions2019

    • Author(s)
      Shiotsugu Shohei、Okinaga Toshinori、Habu Manabu、Yoshiga Daigo、Yoshioka Izumi、Nishihara Tatsuji、Ariyoshi Wataru
    • Journal Title

      Journal of Interferon & Cytokine Research

      Volume: 39 Issue: 11 Pages: 694-702

    • DOI

      10.1089/jir.2019.0034

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ameloblastin attenuates RANKL-mediated osteoclastogenesis by suppressing activation of nuclear factor of activated T cells cytoplasmic1 (NFATc1)2019

    • Author(s)
      Chaweewannakorn W, Ariyoshi W, Okinaga T, Fujita Y, Maki K, Nishihara T
    • Journal Title

      J Cell Physiol

      Volume: 234 Issue: 2 Pages: 1745-1757

    • DOI

      10.1002/jcp.27045

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Accumulation of hyaluronic acid in stromal cells modulates osteoclast formation by regulation of receptor activator of nuclear factor kappa-B ligand expression2019

    • Author(s)
      Nakao Yuko、Hikiji Hisako、Okinaga Toshinori、Takeuchi Jun、Habu Manabu、Yoshiga Daigo、Yoshioka Izumi、Nishihara Tatsuji、Ariyoshi Wataru
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 512 Issue: 3 Pages: 537-543

    • DOI

      10.1016/j.bbrc.2019.03.137

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] パン酵母β-グルカンによるRANKL誘導破骨細胞形成の抑制メカニズム2020

    • Author(s)
      原 詩歌、有吉 渉、京極絵美、吉岡香絵
    • Organizer
      第58回日本小児歯科学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Dectin-1 を介したパン酵母β-グルカンによる破骨細胞形成の抑制メカニズム2020

    • Author(s)
      原 詩歌、有吉 渉、山崎亮太、吉岡香絵
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ATDC5 細胞株の軟骨細胞分化における細胞内シグナルの解析2020

    • Author(s)
      沖田 楓、有吉 渉、吉岡香絵、山崎亮太、引地尚子
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] タンパク分解系を介したTGF-β1 による破骨細胞分化支持能の負の制御機構の解明2020

    • Author(s)
      井上桃子、川元龍夫、有吉 渉
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Evaluation of 3D spheroid culture models of ATDC5 cells in comparison to 2D monolayer cultures2019

    • Author(s)
      Wataru Ariyoshi, Michihiko Usui, Ryota Yamasaki, Yoshie Yoshioka, Sho Mitsugi, Aki Kawano, Keisuke Nakashima, Kohji Nakazawa, Tatsuji Nishihara
    • Organizer
      Asia-Pacific Conference in Fukuoka 2019- International Symposium on Oral Education and Research in Kitakyushu
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 口腔感染症と全身疾患との関連2019

    • Author(s)
      有吉 渉
    • Organizer
      北九州インプラント研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] パン酵母β-グルカンは破骨細胞分化を抑制する2019

    • Author(s)
      原 詩歌、有吉 渉、吉岡香絵、牧 憲司
    • Organizer
      第37回日本小児歯科学会大会 九州地方会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 口腔感染症における歯工学連携研究の応用2019

    • Author(s)
      有吉 渉
    • Organizer
      北九州小児歯科臨床研究会研修会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 各培養条件下でのATDC5細胞株の軟骨細胞分化における細胞内シグナルの解析2019

    • Author(s)
      沖田 楓、有吉 渉、吉岡香絵、山崎亮太、川野亜希、引地尚子
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Involvement of ameloblastin in the regulation of RANKL-induced osteoclast differentiation2018

    • Author(s)
      Wichida Chaweewannakorn、有吉 渉、沖永敏則、牧 憲司、西原達次
    • Organizer
      第56回日本小児歯科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 破骨細胞支持能における内在性ヒアルロン酸の影響2018

    • Author(s)
      中尾優子、有吉 渉、沖永敏則、引地尚子、吉岡 泉、西原達次
    • Organizer
      第78回九州歯科学会総会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Curdlanによるdectin-1の内在化とsykタンパクの分解を介した破骨細胞分化抑制機構2018

    • Author(s)
      有吉 渉、沖永敏則、西原達次
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] アメロブラスチンの破骨細胞分化過程に及ぼす阻害効果2018

    • Author(s)
      Wichida Chaweewannakorn、有吉 渉、沖永敏則、牧 憲司、西原達次
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 内在性ヒアルロン酸が及ぼす破骨細胞支持能への影響について2018

    • Author(s)
      中尾優子、有吉 渉、引地尚子、沖永敏則、西原達次
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      https://www.kyu-dent.ac.jp/research/lecture/infection_molecule

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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