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Signal transduction and functional analysis of TRPM7 in the regulatory mechanism of tooth mineralization

Research Project

Project/Area Number 16H05509
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionFukuoka Dental College

Principal Investigator

okabe koji  福岡歯科大学, 口腔歯学部, 教授 (80224046)

Co-Investigator(Kenkyū-buntansha) 進 正史  福岡歯科大学, 口腔歯学部, 講師 (70549261)
岡本 富士雄  福岡歯科大学, 口腔歯学部, 講師 (60153938)
鍛治屋 浩  福岡歯科大学, 口腔歯学部, 講師 (80177378)
松下 正之  琉球大学, 医学(系)研究科(研究院), 教授 (30273965)
岡 暁子  福岡歯科大学, 口腔歯学部, 准教授 (60452778)
福島 秀文  東北大学, 歯学研究科, 准教授 (70412624)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
KeywordsTRPM7 / エナメル芽細胞 / エナメル質形成 / ミネラル輸送 / キナーゼ / エナメル質石灰化 / 歯の石灰化 / 象牙芽細胞 / 歯の形成
Outline of Final Research Achievements

Channel kinase TRPM7 is a unique bi-functional cation channel containing a protein kinase domain and highly expressed in teeth. Using ameloblast-specific TRPM7 conditional knock out (cKO) mice and TRPM7 kinase mutant (KR) mice, the function of mineral transport and kinase activity of TRPM7 in tooth formation was investigated. In KR mice, the channel function of TRPM7 in ameloblasts was normal, but the minor enamel defects with hypomineralization and decreased phosphorylation of BMP signal molecules were observed. On the other hand, cKO mice showed the severe enamel hypomineralization and abnormal ameloblast morphology together with suppression of
TRPM7 ion transport. Therefore, it was found that both TRPM7 ion transport and kinase activity contribute to enamel formation through modulation of ameloblast differentiation and cell morphology.

Academic Significance and Societal Importance of the Research Achievements

歯の石灰化過程を担うミネラル輸送の分子同定や石灰化機構に関しては多くが不明であり解明すべき必須課題である。本研究の学術的意義は、生体において最もエナメル芽細胞に高発現するミネラル輸送体TRPM7に注目し、歯の細胞特異的な遺伝子改変マウスを用いて、これまで困難であった歯の石灰化調節の分子機構解明に取組む点である。これらの取組は、歯の形成異常を特徴とする病態機序を解く上でも重要であり、歯の再生研究の基盤形成や創薬開発に向けての展開への社会的貢献にもつながると考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (22 results)

All 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (13 results) (of which Invited: 1 results) Remarks (3 results)

  • [Journal Article] Toll-like receptor 2 activation primes and upregulates osteoclastogenesis via lox-1.2018

    • Author(s)
      Ohgi K, Kajiya H, Goto-T K, Okamoto F, Yoshinaga Y, Okabe K, Sakagami R
    • Journal Title

      Lipids Health Dis.

      Volume: 17(1) Issue: 1 Pages: 132-132

    • DOI

      10.1186/s12944-018-0787-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab44, a novel large Rab GTPase, negatively regulates osteoclast differentiation by modulating intracellular calcium levels followed by NFATc1 activation.2018

    • Author(s)
      Yu Yamaguchi, Eiko Sakai, Kuniaki Okamoto, Hiroshi Kajiya, Koji Okabe, Mariko Naito, Tomoko Kadowaki and Tsukuba T
    • Journal Title

      Cell Mol Life Sci.

      Volume: 75 Issue: 1 Pages: 33-48

    • DOI

      10.1007/s00018-017-2607-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The crucial role of the TRPM7 kinase domain in the early stage of amelogenesis.2017

    • Author(s)
      Ogata K, Tsumuraya T, Oka K, Shin M, Okamoto F, Kajiya H, Katagiri C, Ozaki M, Matsushita M, Okabe K.
    • Journal Title

      Sci Rep.

      Volume: 22;7(1) Pages: 18099-18099

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The SCFβ-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis.2017

    • Author(s)
      Shimizu K, Fukushima H, Ogura K, Lien EC, Nihira NT, Zhang J, North BJ, Guo A, Nagashima K, Nakagawa T, Hoshikawa S, Watahiki A, Okabe K, Yamada A, Toker A, Asara JM, Fukumoto S, Nakayama KI, Nakayama K, Inuzuka H, Wei W.
    • Journal Title

      Sci Signal. doi: 10.1126/scisignal.aah4117.

      Volume: 10 Issue: 460 Pages: 1-15

    • DOI

      10.1126/scisignal.aah4117

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hyperocclusion stimulates the expression of collagen type XII in periodontal ligament.2016

    • Author(s)
      Tsuzuki T, Kajiya H, T-Goto K, Tsutsumi T, Nemoto T, Okabe K, Takahashi Y.
    • Journal Title

      Arch Oral Biol.

      Volume: 66 Pages: 86-91

    • DOI

      10.1016/j.archoralbio.2016.02.009

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN couplex localization and promotes renal cancer progression2016

    • Author(s)
      Nagashima, K., Fukushima, H., Shimizu, K., Hidaka, M., Hasumi, H., Ikebe, T., Fukumoto, S., Okabe, K., Inuzuka, H.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 6 Pages: 9947-9960

    • DOI

      10.18632/oncotarget.14221

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 間葉系細胞由来TRPM7による骨格形成制御2018

    • Author(s)
      進 正史・溝口利英・岡本富士雄・鍛治屋 浩・岡部幸司
    • Organizer
      第36回骨代謝学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウスエナメル芽細胞の新規標識・分取法2018

    • Author(s)
      進 正史・岡本富士雄・鍛治屋 浩・原田英光・岡部幸司
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] TRPM7によるエナメル質形成制御2018

    • Author(s)
      進 正史・岡本富士雄・鍛治屋 浩・岡部幸司
    • Organizer
      第69回西日本生理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] エナメル芽細胞蛍光標識モデルの開発2018

    • Author(s)
      進 正史・岡本富士雄・鍛治屋 浩・岡部幸司
    • Organizer
      第45回福岡歯科大学学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] エナメル質形成におけるTRPM7のキナーゼ活性とチャネル機能の意義2018

    • Author(s)
      進 正史、緒方佳代子、圓谷 智之、岡 暁子、岡本富士雄、鍛治屋 浩、片桐千秋、尾崎正雄、松下正之、岡部幸司
    • Organizer
      第95回日本生理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TRPM7のキナーゼドメインを介したエナメル質形成制御2017

    • Author(s)
      進 正史、緒方佳代子、岡 暁子、岡本富士雄、鍛治屋 浩、岡部幸司
    • Organizer
      第35回日本骨代謝学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] MMP20過剰発現はエナメル芽細胞の細胞極性障害によりエナメル質形成不全を呈する2017

    • Author(s)
      進 正史、岡本富士雄、鍛治屋 浩、緒方佳代子、岡部幸司
    • Organizer
      第59回歯科基礎医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TRPM7キナーゼを介するリン酸化シグナルとエナメル質形成制御2017

    • Author(s)
      進 正史、緒方佳代子、圓谷智之、岡 暁子、岡本富士雄、鍛治屋 浩、片桐千秋、尾崎正雄、松下正之、岡部幸司
    • Organizer
      第68回西日本生理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経堤細胞特異的TRPM7欠損マウスを用いた歯の発達におけるTRPM7の役割解析2017

    • Author(s)
      緒方佳代子,岡 暁子,進 正史,岡本富士雄,鍛冶屋 浩,尾崎正雄, 岡部幸司
    • Organizer
      第44回福岡歯科大学学会総会・学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] エナメル質石灰化に関わるTRPチャネルの発現と機能2016

    • Author(s)
      岡部幸司、緒方佳代子、進 正史、岡本富士雄、岡 暁子、鍛治屋 浩
    • Organizer
      第58回歯科基礎医学会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] エナメル質形成におけるプロテアーゼの役割2016

    • Author(s)
      進 正史、岡本富士雄、鍛治屋 浩、緒方佳代子、岡部幸司
    • Organizer
      第58回歯科基礎医学会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] SCFβ-TRCP依存的なFNIP2タンパク質の量的変化はmTORCシグナル制御とBHD症候群の病態に寄与する2016

    • Author(s)
      永嶌勝之、福島秀文、星川聖良、綿引麻美、福本 敏、岡部幸司
    • Organizer
      第58回歯科基礎医学会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] MMP20はcadhelineのシグナル調節を介してエナメル質形成を制御する2016

    • Author(s)
      進 正史、岡本富士雄、鍛治屋 浩、緒方佳代子、岡部幸司、バートレット・ジョン
    • Organizer
      第34回日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Remarks] 福岡学園・学術情報データーベース

    • URL

      https://acinfo.college.fdcnet.ac.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 福岡学園 学術データーベース

    • URL

      http://www.college.fdcnet.ac.jp

    • Related Report
      2017 Annual Research Report
  • [Remarks] 福岡学園 学術データーベース

    • URL

      http://www.college.fdcnet.ac.jp/

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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