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Osteoclast activator: a promising therapeutic target for osteoporosis

Research Project

Project/Area Number 15K15683
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional basic dentistry
Research InstitutionNiigata University

Principal Investigator

SAEKI Makio  新潟大学, 医歯学系, 教授 (30273692)

Co-Investigator(Kenkyū-buntansha) 柿原 嘉人  新潟大学, 医歯学系, 助教 (40379938)
Co-Investigator(Renkei-kenkyūsha) YOSHIZAWA Michiko  松本歯科大学, 歯学部, 教授 (60303137)
Research Collaborator AKIBA Yosuke  新潟大学, 医歯学総合病院, 講師 (70547512)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords骨再生 / 破骨細胞 / 骨吸収 / NFAT / RANKL / 骨
Outline of Final Research Achievements

Small molecule compounds that potently affect osteoclastogenesis could be useful as chemical probes for elucidating the mechanisms of various biological phenomena, and as effective therapeutic strategies against bone resorption. An osteoclast progenitor cell-based high-throughput screening system was designed to target activation of nuclear factor of activated T cells (NFAT), which is a key event for osteoclastogenesis. Chemical compound library screening using this system identified kenpaullone, to be an NFAT regulator in osteoclasts. Kenpaullone promoted receptor activator for NF-κB ligand (RANKL)-induced NFAT activity in RAW264.7 cells and also promoted the formation of TRAP-positive multinucleated osteoclasts from RAW264.7 cells and mouse primary bone marrow macrophages (BMMs) in a concentration-dependent manner.

Report

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

    (5 results)

All 2016 2015

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

  • [Journal Article] The inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis.2016

    • Author(s)
      Akiba Y, Mizuta A, Kakihara Y, Nakata J, Nihara J, Saito I, Egusa H, Saeki M
    • Journal Title

      BB reports

      Volume: 5 Pages: 253-258

    • DOI

      10.1016/j.bbrep.2015.12.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] GSK-3β inhibitory activities of novel dichroloresorcinol derivatives from Cosmospora vilior isolated from a mangrove plant2016

    • Author(s)
      Yoshihito Shiono, Nozomi Miyazaki, Tetsuya Murayama, Takuya Koseki, Harizon, Dewa Gede Katja, Unang Supratman, Juri Nakata, Yoshito Kakihara, Makio Saeki, Jun Yoshida, Shota Uesugi, Ken-ichi Kimura
    • Journal Title

      Phytochemistry Letters

      Volume: 18 Pages: 122-127

    • DOI

      10.1016/j.phytol.2016.09.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] he inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis2016

    • Author(s)
      Akiba Y, Mizuta A, Kakihara Y, Nakata J, Nihara J, Saito I, Egusa H, Saeki M
    • Journal Title

      BB reports

      Volume: 5 Pages: 253-258

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 破骨細胞分化に影響を与える薬剤のスクリーニングとその作用機序の解析2016

    • Author(s)
      中田樹里、柿原嘉人、秋葉陽介、丹原惇、齋藤功、佐伯万騎男
    • Organizer
      第34回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-07-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新規抗癌標的分子としてのR2TP複合体2015

    • Author(s)
      佐伯万騎男
    • Organizer
      第17回応用薬理シンポジウム
    • Place of Presentation
      有壬記念館(新潟県・新潟市)
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2018-03-22  

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