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Therapeutic strategies against bone resorption using calcineurin signaling in osteoclast

Research Project

Project/Area Number 20592172
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

SAEKI Makio  Osaka University, 大学院・歯学研究科, 講師 (30273692)

Co-Investigator(Kenkyū-buntansha) KAMISAKI Yoshinori  大阪大学, 大学院・歯学研究科, 教授 (40116017)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords破骨細胞 / NFATc1 / スクリーニング / 小分子化合物 / harmine / id2 / カルシニューリン / NFAT / 骨 / RANKL / Harmine / アポトーシス / PICK1
Research Abstract

Small molecular compounds that potently affect osteoclastogenesis could be useful as a chemical probe for elucidating the mechanism of biological phenomena and form the basis for effective therapeutic strategies against bone resorption. To establish a high-throughput screening system for identifying osteoclastogenesis-related compounds using a cell-based sensor, and to identify novel chemical entities regulating signaling pathways in osteoclasts. Harmine activates NFATc1 expression independent of RANKL stimulation, as well as enhanced Id2 expression in osteoclast precursor cells. These multimodal actions of harmine may overall suppress osteoclastogenesis.

Report

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

    (40 results)

All 2011 2010 2009 2008 Other

All Journal Article (13 results) (of which Peer Reviewed: 12 results) Presentation (27 results)

  • [Journal Article] RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-Kappa B pathway2011

    • Author(s)
      Shimada K, Saeki M, Egusa H, Fukuyasu S, Yura Y, Iwai K, Kamisaki Y
    • Journal Title

      Biochem.Biophys.Res.Comm. 404

      Pages: 910-914

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-Kappa B pathway2011

    • Author(s)
      Shimada K, Saeki M, Egusa H, Fukuyasu S, Yura Y, Iwai K.Kamisaki Y
    • Journal Title

      Biochem Biophys Res Comm

      Volume: 404 Pages: 910-914

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PIH1D1, a subunit of R2TP complex, inhibits doxorubicin-induced apoptosis2010

    • Author(s)
      Inoue M, Saeki M, Egusa H, Niwa H, Kamisaki Y
    • Journal Title

      Biochem.Biophys.Res.Comm. 403

      Pages: 340-344

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] PIH1D1,a subunit of R2TP complex, inhibits doxorubicin-induced apoptosis2010

    • Author(s)
      Inoue M, Saeki M, Egusa H, Niwa H, Kamisaki Y
    • Journal Title

      Biochem Biophys Res Comm

      Volume: 403 Pages: 340-344

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of myeloid cell leukemia-1in cell growth of squamous cell carcinoma2009

    • Author(s)
      Nagata M, Wada K, Nakajima A, Nakajima N, Kusayama M, Masuda T, Iida S, Okura M, Kogo M, Kamisaki Y
    • Journal Title

      J.Pharmacol.Sci. 110

      Pages: 344-353

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] RPAP3 interacts with Reptin to regulate UV-induced phosphorylation of H2AX and DNA damage2009

    • Author(s)
      Ni L, Saeki M, Xu L, Nakahara H, Saijo M, Tanaka K, Kamisaki Y
    • Journal Title

      J.Cellular Biochemistry 106

      Pages: 920-928

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] RPAP3 interacts with Reptin to regulate UV-induced phosphorylation of H2AX and DNA damage2009

    • Author(s)
      Ni L, Saeki M, Xu L, Nakahara H, Saijo M., Tanaka K, Kamisaki Y
    • Journal Title

      J.Cellular Biochemistry 106

      Pages: 920-928

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced bone regeneration via multimodal actions of synthetic peptide SVVYGLR on osteoprogenitors and osteoclasts2009

    • Author(s)
      Egusa H, Kaneda Y, Akashi Y, Hamada Y, Matsumoto T, Saeki M, Thakor DK, Tabata Y, Matsuura N, Yatani H.
    • Journal Title

      Biomaterials 30

      Pages: 4676-4686

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning of novel Monad binding protein containing tetratricopeptide repeat domains2008

    • Author(s)
      Itsuki Y, Saeki M, Nakahara H, Egusa H, Irie Y, Terao Y, Kawabata S, Yatani H, Kamisaki Y
    • Journal Title

      FEBS Letters 582

      Pages: 2365-2370

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning of nove 1 Monad binding prote in containing tetratricopeptide repeat domains2008

    • Author(s)
      Itsuki Y, Saeki M, Nakahara H, Egusa H, Irie Y, Terao Y, Kawabata S, Yatani H, Kamisaki Y
    • Journal Title

      FEBS Letters 582

      Pages: 2365-2370

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 新規遺伝子Monadのアポトーシスにおける役割2008

    • Author(s)
      佐伯万騎男
    • Journal Title

      大阪大学歯学雑誌 53

      Pages: 5-6

    • NAID

      10026062372

    • Related Report
      2008 Annual Research Report
  • [Journal Article] PICKI binds to calcineurin B and modulates the NFAT activity in PC12 cells2008

    • Author(s)
      Iida t, Egusa H, Saeki M, Yatani H, Kamisaki Y
    • Journal Title

      BBRC 375

      Pages: 655-659

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The small molecule harmine regulates NFATc1 and Id2 expression in osteoclast progenitor cells

    • Author(s)
      Egusa H, Doi M, Saeki M, Fukuyasu S, Akashi Y, Yokota Y, Yatani H, Kamisaki Y
    • Journal Title

      Bone in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] Chemical library screening of orphan ligands for identifying osteoclastogenesis -related small molecular compounds2011

    • Author(s)
      佐伯万騎男、上崎善規
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Chemical library screening of orphan ligands for identifying osteoclas togenesis-related small molecular compounds2011

    • Author(s)
      Makio Saeki, Yoshinori Kamisaki
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report
  • [Presentation] RNA polymerase II-associated protain3はNFκB活性を抑制しドキソルビシン誘導性アポトーシスを増強する2010

    • Author(s)
      島田佳奈、井上美香、佐伯万騎男、江草宏、由良義明、上崎善規
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Monadはヒト乳がん細胞MDA-MB-231細胞の浸潤能を負に制御する2010

    • Author(s)
      成清綾、吉田好紀、佐伯万騎男、井上美香、島田佳奈、江草宏、丹羽均、由良義明、矢谷博文、上崎善規
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-19
    • Related Report
      2010 Final Research Report
  • [Presentation] 扁平上皮癌におけるエンドセリン受容体シグナルの役割2010

    • Author(s)
      石本俊介、和田孝一郎、大倉正也、古郷幹彦、上崎善規
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-19
    • Related Report
      2010 Final Research Report
  • [Presentation] 口腔扁平上皮ガンにおける細胞接着分子キゼリン/CD146の発現と役割2010

    • Author(s)
      小浜恵子、和田孝一郎、平英一、上崎善規
    • Organizer
      第117回日本薬理学会近畿部会
    • Place of Presentation
      徳島
    • Year and Date
      2010-07-08
    • Related Report
      2010 Final Research Report
  • [Presentation] RPAP3 promotes doxorubicin-induced apoptosis in human breast cancer T-47D cells2010

    • Author(s)
      堀内華奈, 井上美香, 佐伯万騎男, 江草宏, 由良義明, 上崎善規
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Monad binding protein-2 interacts with RPAP3 and regulates doxorubicin-induced apoptosis in U2OS cell2010

    • Author(s)
      井上美香, 堀内華奈, 佐伯万騎男, 江草宏, 丹羽均, 上崎善規
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-16
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Role of Aquaporin-3 squamous cell carcinoma2010

    • Author(s)
      Kusayama M, Wada K, Okura M, Kogo M, Kamisaki Y
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Monadは乳癌細胞の浸潤を抑制する2010

    • Author(s)
      Makio Saeki Yoshinori Kamisaki
    • Organizer
      第52回歯科基礎医学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2010 Annual Research Report
  • [Presentation] RPAP3 promotes doxorubicin-induced apoptosis in human Breast cancer T-47D cells2010

    • Author(s)
      Horiuchi K, Inoue M, Saeki M, Hiroshi M, Egusa H, Yura T, Kamisaki Y
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] RPAP3およびMonad binding protein2(MBP2)のアポトーシスにおける役割2009

    • Author(s)
      井上美香、堀内華奈、佐伯万騎男、江草宏、丹羽均、上崎善規
    • Organizer
      第116回日本薬理学会近畿部会
    • Place of Presentation
      大津
    • Year and Date
      2009-11-13
    • Related Report
      2010 Final Research Report
  • [Presentation] 扁平上皮癌におけるAquaporin3の役割2009

    • Author(s)
      草山守生、和田孝一郎、永田雅英、飯田征二、大倉正也、古郷幹彦、上崎善規
    • Organizer
      第116回日本薬理学会近畿部会
    • Place of Presentation
      大津
    • Year and Date
      2009-11-13
    • Related Report
      2010 Final Research Report
  • [Presentation] RPAP3および Monad binding protein2 (MBP2) のアポトーシスにおける役割2009

    • Author(s)
      井上美香, 堀内華奈, 佐伯万騎男, 江草宏, 丹羽均, 上崎善規
    • Organizer
      第116回日本薬理学会近畿部会
    • Place of Presentation
      滋賀
    • Year and Date
      2009-11-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] Monad関連遺伝子のドキソルビシン誘導性アポトーシスヘ及ぼす影響2009

    • Author(s)
      堀内華奈, 井上美香, 佐伯万騎男, 江草宏, 由良義明, 上崎善規
    • Organizer
      第109回大阪大学歯学会例会
    • Place of Presentation
      大阪
    • Year and Date
      2009-11-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] U2OS細胞における Monad 結合蛋白質RPAP3のアポトーシスへの関与2009

    • Author(s)
      井上美香, 堀内華奈, 佐伯万騎男, 江草宏, 丹羽均, 上崎善規
    • Organizer
      第108回大阪大学歯学会例会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 小分子化合物 harmine は破骨前駆細胞におけるNEATc1及びId2発現を増強する2009

    • Author(s)
      土居正典, 江草宏, 佐伯万騎男, 矢谷博文, 上崎善槻
    • Organizer
      第108回大阪大学歯学会例会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Role of Monad binding protein 1 in UV-induced DNA damage2009

    • Author(s)
      Saeki M, Ni L, Kamisaki Y
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] Mcl-1 as a target for the therapy of squamous cell carcinoma2009

    • Author(s)
      Nagata M, Wada K, Kusayama M, Iida S, Okura M, Kogo M, Kamisaki Y
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2010 Final Research Report
  • [Presentation] 小分子化合物 harmine は破骨前駆細胞におけるNFATc1及びId2発現を増強する2009

    • Author(s)
      江草宏, 土居正典, 佐伯万騎男, 矢谷博文
    • Organizer
      第27回日本骨代謝学会学術大会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] 扁平上皮癌におけるMyeloid cell leukemia-1発現抑制による抗癌剤の作用増強2008

    • Author(s)
      永田雅英、和田孝一郎、草山守生、大倉正也、古郷幹彦、上崎善規
    • Organizer
      第114回日本薬理学会近畿部会
    • Place of Presentation
      神戸
    • Year and Date
      2008-11-14
    • Related Report
      2010 Final Research Report
  • [Presentation] NFTAc1をターゲットとした破骨細胞分化関連化合物の探索2008

    • Author(s)
      土居正典, 佐伯万騎男, 江草宏, 矢谷博文, 上崎善規
    • Organizer
      第114回日本薬理学会近畿部会
    • Place of Presentation
      神戸
    • Year and Date
      2008-11-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] 口腔扁平上皮癌細胞の増殖におけるMyeloid cell leukemia-1の役割2008

    • Author(s)
      永田雅英、和田孝一郎、草山守生、古郷幹彦、上崎善規
    • Organizer
      第50回歯科基礎医学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-23
    • Related Report
      2010 Final Research Report
  • [Presentation] Monad結合蛋白質Monad binding protein 1のアポトーシス増強作用2008

    • Author(s)
      伊月悠貴, 佐伯万騎男, 江草宏, 矢谷博文, 上崎善規
    • Organizer
      第106回大阪大学歯学会例会
    • Place of Presentation
      大阪
    • Year and Date
      2008-07-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Monad結合蛋白質Monad binding proteinl / RPAP3のアポトーシス増強作用2008

    • Author(s)
      伊月悠貴, 佐伯万騎男, 入江康至, 西條詩文, 田中亀代次, 江草宏, 矢谷博文, 上崎善規
    • Organizer
      第113回日本薬理学会近畿部会
    • Place of Presentation
      岡山
    • Year and Date
      2008-06-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] Involvement of Calcineurin and PICKl in RANKL-induced osteoclast Differentiaion2008

    • Author(s)
      Iida T, Egusa H, Saeki M, Doi M. Kamisaki Y, Yatani H
    • Organizer
      86 th General Session &Exhibition of the IADR
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2008 Annual Research Report
  • [Presentation] Harmineの破骨細胞分化へ及ぼす作用2008

    • Author(s)
      土居正典, 江草宏, 佐伯万騎男, 飯田務, 上崎善規, 矢谷博文
    • Organizer
      第50回歯科基礎医学会学術大会ならびに総会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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