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Analysis of the molecular mechanism of signal transduction emanated from receptor RANK which regulates osteoclastogenesis

Research Project

Project/Area Number 25861297
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

TAGUCHI Yuu  東京大学, 医科学研究所, 助教 (20549472)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords骨免疫学 / 骨代謝 / 破骨細胞 / RANK / 骨免疫
Outline of Final Research Achievements

Since excess formation and differentiation of osteoclasts, which have an ability to resorb bone matrix, cause bone diseases such as osteoporosis and bone metastasis, elucidating the molecular mechanism of osteoclastogenesis is very significant for developing the novel method for treating bone diseases. In this study, candidate proteins were identified as binding protein to HCR, which is essential region in receptor RANK for induction of osteoclastogenic signaling. As a result, I found the novel signaling pathway in RANK signaling for osteoclastogenesis. Treatment osteoclast precursor cells with peptides corresponding to amino acid sequences of HCR inhibit osteoclastogenesis, suggesting that osteoclastogenesis can be controlled artificially. Furthermore, the novel gene was indentified as suppressor for osteoclastogenesis. These results should be helpful for developing the novel drug and treating methods against bone disease.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (19 results)

All 2015 2014 2013

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (18 results)

  • [Journal Article] NF-κB non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype.2013

    • Author(s)
      Yamamoto, M
    • Journal Title

      Nat. Commun.

      Volume: 4 Issue: 1 Pages: 2299-2299

    • DOI

      10.1038/ncomms3299

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Transcriptional regulation by the oscillatory dynamics of non-canonical NF-κB2015

    • Author(s)
      Takao Seki, Daisuke Ohshima, Yuu Taguchi, Taishin Akiyama, Kazuhisa Ichikawa, Jun-ichiro Inoue
    • Organizer
      がん研究分野の特性等を踏まえた支援活動公開シンポジウム
    • Place of Presentation
      一橋講堂 (東京都・千代田区)
    • Year and Date
      2015-01-27 – 2015-01-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Transcriptional regulation by the oscillatory dynamics of non-canonical NF-κB2015

    • Author(s)
      Takao Seki, Daisuke Ohshima, Yuu Taguchi, Taishin Akiyama, Kazuhisa Ichikawa, Jun-ichiro Inoue
    • Organizer
      「修飾シグナル病」第2回国際シンポジウム
    • Place of Presentation
      東京大学医科学研究所 (東京都・港区)
    • Year and Date
      2015-01-23 – 2015-01-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 受容体RANKの刺激依存的な細胞内への局在と、破骨細胞分化におけるその役割2014

    • Author(s)
      田口 祐、井上 純一郎
    • Organizer
      第37回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県・横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] TRAF6ポリユビキチン化を抑制する低分子化合物のシグナル伝達阻害と抑制メカニズムに関する検討2014

    • Author(s)
      古賀 涼子、江島 智彦、金丸 陽亮、柴田 佑里、田口 祐、井上 純一郎、 大塚 雅巳、 藤田 美歌子
    • Organizer
      第37回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県・横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 非古典的NF-kB経路の振動による転写抑制メカニズムの解析2014

    • Author(s)
      関 崇生、大島 大輔、 田口 祐、秋山 泰身、 市川 一寿、 井上 純一郎
    • Organizer
      第37回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県・横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 受容体RANKの刺激依存的な細胞内への局在と、破骨細胞分化におけるその役割2014

    • Author(s)
      田口 祐、井上 純一郎
    • Organizer
      修飾シグナル病 若手ワークショップ
    • Place of Presentation
      (神奈川県・湯河原市)
    • Year and Date
      2014-09-30 – 2014-10-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] The internalization of RANK is crucial for differentiation of osteoclast involved in bone metastasis2014

    • Author(s)
      Yuu Taguchi, Jun-ichiro Inoue
    • Organizer
      第73回 日本癌学会学術集会
    • Place of Presentation
      パシフィコ横浜 (神奈川県・横浜市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] The stimulation-dependent internalization of RANK is crucial for osteoclast differentiation2014

    • Author(s)
      Yuu Taguchi, Jun-ichiro Inoue
    • Organizer
      ASBMR 2014 Annual Meeting
    • Place of Presentation
      Houston (USA)
    • Year and Date
      2014-09-12 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 転写因子NF-kBの時空間的制御メカニズムの解析2014

    • Author(s)
      関 崇生、大島 大輔、田口 祐、山口 憲孝、合田 仁、秋山 泰身、市川 一寿、井上 純一郎
    • Organizer
      平成26年度 がん若手研究者ワークショップ
    • Place of Presentation
      蓼科グランドホテル滝の湯 (長野県・茅野市)
    • Year and Date
      2014-09-03 – 2014-09-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 受容体RANKの刺激依存的な細胞質内への局在化と、その破骨細胞分化における役割2014

    • Author(s)
      田口 祐、井上 純一郎
    • Organizer
      第32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
      2014-07-24 – 2014-07-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of dynamic regulation of the non-canonical NF-κB activation2014

    • Author(s)
      Takao Seki, Daisuke Oshima, Yuu Taguchi, Noritaka Yamaguchi, Jin Gohda, Taishin Akiyama, Kazuhisa Ichikawa, Jun-ichiro Inoue
    • Organizer
      IMSUT研究成果発表会
    • Place of Presentation
      東京大学医科学研究所 (東京都・港区)
    • Year and Date
      2014-05-30 – 2014-06-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] RANK Harbors the specific cytoplasmic domain that regulates osteoclastogenic signaling and its subcellular localization2013

    • Author(s)
      Yuu TAGUCHI, Jun-ichiro INOUE
    • Organizer
      International Bone & Mineral Society・2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
    • Place of Presentation
      神戸国際会議場、ポートピアホテル
    • Related Report
      2013 Research-status Report
  • [Presentation] Genetic screening of Novel Negative Regulators in osteoclast differentiation2013

    • Author(s)
      Fukutoshi SHIRAI, Jin GOHDA, Shinya WATANABE, Kentaro SEMBA, Yuu TAGUCHI, Jun-ichiro INOUE
    • Organizer
      International Bone & Mineral Society・2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
    • Place of Presentation
      神戸国際会議場、ポートピアホテル
    • Related Report
      2013 Research-status Report
  • [Presentation] Identification of proteins binding to the unique domain in RANK required to establish osteoclastogenic signals2013

    • Author(s)
      Kazuaki TSUMURA, Yuu TAGUCHI, Masaaki OYAMA, Hiroko KOZUKA-HATA, Jun-ichiro INOUE
    • Organizer
      International Bone & Mineral Society・2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
    • Place of Presentation
      神戸国際会議場、ポートピアホテル
    • Related Report
      2013 Research-status Report
  • [Presentation] RANK has the unique domain that induces its internalization possibly required for osteoclastogenesis2013

    • Author(s)
      田口 祐、合田 仁、井上 純一郎
    • Organizer
      新学術領域「がん研究分野の特性等を踏まえた支援活動」・がん若手研究者ワークショップ
    • Place of Presentation
      蓼科グランドホテル滝の湯
    • Related Report
      2013 Research-status Report
  • [Presentation] RANK has the unique domain that induces its internalization possibly required for osteoclastogenesis.2013

    • Author(s)
      Yuu TAGUCHI and Jun-ichiro INOUE
    • Organizer
      第72回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 受容体RANKのRANKL刺激依存的な細胞内取り込みとその破骨細胞分化における役割2013

    • Author(s)
      田口 祐、井上 純一郎
    • Organizer
      新学術領域「修飾シグナル病」・第2回若手ワークショップ
    • Place of Presentation
      伊香保温泉 森秋旅館
    • Related Report
      2013 Research-status Report
  • [Presentation] stimulation-dependent internalization of RANK is required for the cell-cell fusion during osteoclastogenesis2013

    • Author(s)
      Yuu TAGUCHI, Jun-ichiro INOUE
    • Organizer
      The 9th China-Japan Joint Laboratory Workshop
    • Place of Presentation
      中国科学院微生物研究所、中国
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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