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Investigation of bone resorption by osteoclasts : aiming at therapy regulating osteoclastic bone resorption.

Research Project

Project/Area Number 20590321
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionHimeji Dokkyo University

Principal Investigator

TOHYAMA Yumi  Himeji Dokkyo University, 薬学部, 教授 (70362770)

Co-Investigator(Kenkyū-buntansha) 梶本 武利  姫路獨協大学, 薬学部, 講師 (00509953)
Co-Investigator(Renkei-kenkyūsha) KAJI Hiroaki  姫路獨協大学, 薬学部, 講師 (10368706)
TANAKA Chisato  姫路獨協大学, 薬学部, 助手 (30461122)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords破骨細胞 / リソソーム / ATP / P2X7 / Syk / Rab27a / 核酸受容体 / アセチル化 / 細胞骨格 / チロシンキナーゼ
Research Abstract

Osteoclasts are bone-degrading cells playing an exclusive role in bone remodeling but molecular mechanism of osteolysis is poorly understood. Here we established a traceable and reproducible in vitro analyzing system for osteolysis using human osteoclasts because we found that an energy molecule ATP acts as a specific osteolysis initiator via P2X7-nucleotide receptor. We further show that deacetylation of α-tubulin is a critical reaction for osteolysis. Pharmacological inhibition of α-tubulin deacetylation resulted in defective bone resorption, accompanied by (1) failure of sealing-zone formation and (2) ceased secretion of osteolytic granules. Furthermore, kinetics of deacetylation was found to be regulated by Syk. These data suggest a novel P2X7-Syk-acetylation/deacetylation pathway for therapeutic targets in osteolytic diseases.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (21 results)

All 2011 2010 2009 2008 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (7 results) Remarks (4 results)

  • [Journal Article] Rab27a negatively regulates phagocytosis by prolongation of the actin-coating stage around phagosomes2011

    • Author(s)
      Yokoyama K, Kaji H, He J, Tanaka C, Hazama R, Kamigaki T, Ku Y, Tohyama K, Tohyama Y
    • Journal Title

      J Biol Chem. 286

      Pages: 5375-5382

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rab27a negatively regulates phagocytosis by prolongation of the actin-coating stage around phagosomes.2011

    • Author(s)
      Yokoyama K
    • Journal Title

      J Biol Chem.

      Volume: 286 Pages: 5375-5382

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase C delta-specific activity reporter reveals agonist-evoked nuclear activity controlled by Src family of kinases2010

    • Author(s)
      Kajimoto T, Sawamura S, Tohyama Y, Mori Y, Newton AC
    • Journal Title

      J Biol Chem. 285

      Pages: 41896-41910

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis.2010

    • Author(s)
      Matsuoka A, Tochigi A, Kishimoto M, Nakahara T, Kondo T, Tsujioka T, Tasaka T, Tohyama Y, Tohyama K
    • Journal Title

      Leukemia. 24

      Pages: 748-755

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase C {delta}-specific activity reporter reveals agonist-evoked nuclear activity controlled by Src family of kinases.2010

    • Author(s)
      Kajimoto T
    • Journal Title

      J Biol Chem.

      Volume: 285 Pages: 41896-41910

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ATP-induced osteoclast function ; the formation of sealing-zone like structure and the secretion of lytic granules via microtubule-deacetylation under the control of Syk.2009

    • Author(s)
      Hazama R, Qu X, Yokoyama K, Tanaka C, Kinoshita E, He J, Takahashi S, Tohyama K, Yamamura H, Tohyama Y
    • Journal Title

      Genes to Cells 14

      Pages: 871-884

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein-Tyrosine Kinase, Syk : A Key Player in Phagocytic cells2009

    • Author(s)
      Tohyama Y, Yamamura H
    • Journal Title

      J Biochem. 145(Review)

      Pages: 267-273

    • NAID

      10024914735

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ATP-induced osteoclast function ; the formation of sealing-zone like structure and the secretion of lytic granules via microtubule-deacetylation under the control of Syk2009

    • Author(s)
      Ryoichi Hazama
    • Journal Title

      Genes to Cells 14

      Pages: 871-884

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein-Tyrosine Kinase, Syk : A Key Player in Phagocytic Cells.2009

    • Author(s)
      Yumi Tohyama
    • Journal Title

      The Journal of Biochemistry. 145

      Pages: 267-273

    • NAID

      10024914735

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Validation of the revised 2008 WHO diagnostic criteria in 75 suspected cases of myeloproliferative neoplasm.2008

    • Author(s)
      Kondo T, Okuno N, Naruse H, Kishimoto M, Tasaka T, Tsujioka T, Matsuoka A, Sugihara T, Tohyama Y, Tohyama K
    • Journal Title

      Leuk Lymphoma. 49

      Pages: 1784-1791

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] ATP-induced bone resorption in osteoclasts : the formation of sealing-zone like structure and the secretion of lytic granules via Syk dependent deacetylation of alpha tubulin.2010

    • Author(s)
      Yumi Tohyama, Hirohei Yamamura
    • Organizer
      第14回 国際免疫学会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2010-08-26
    • Related Report
      2010 Final Research Report
  • [Presentation] ATP-induced bone resorption in osteoclasts : the formation of sealing-zone like structure and the secretion of lytic granules via Syk dependent deacetylation of alpha tubulin2010

    • Author(s)
      Yumi Tohyama(通山由美)
    • Organizer
      第14回 国際免疫学会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-08-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 破骨細胞においてATP/P2X7受容体シグナルにより誘導される微小管のアセチル化制御を介した骨吸収の分子機構の解析2010

    • Author(s)
      陌間亮一,通山由美
    • Organizer
      第28回 日本骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2010-07-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 破骨細胞においてATP/P2X_7受容体シグナルにより誘導される微小管のアセチル化制御を介した骨吸収の分子機構の解析2010

    • Author(s)
      陌間亮一
    • Organizer
      日本骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2010-07-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] ATP/P2X7シグナリングを介した破骨細胞による骨吸収機構の解析2009

    • Author(s)
      陌間亮一,山村博平,通山由美
    • Organizer
      第82回 日本生化学会大会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2009-10-22
    • Related Report
      2010 Final Research Report
  • [Presentation] ATP/P2X_7シグナリングを介した破骨細胞による骨吸収機構の解析2009

    • Author(s)
      陌間亮一
    • Organizer
      日本生化学会大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 巨核球分化におけるRab27Bの機能解析2009

    • Author(s)
      田中千都
    • Organizer
      日本薬学会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2009-03-27
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.himeji-du.ac.jp/faculty/dp_pharm/pharm/pt2/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.himeji-du.ac.jp/faculty/dp_pharm/pharm/pt2/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.himeji-du.ac.jp/faculty/dp_pharm/pharm/pt2/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.himeji-du.ac.jp/faculty/pharm/pharm/pt2/index.html

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2019-01-07  

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