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Elucidation of the mechanism that new osteoblastic activating factors control bone metabolisms for preventing a relapse after the orthodontic treatment

Research Project

Project/Area Number 18K09861
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionKyushu Dental College

Principal Investigator

Kuroishi Kayoko  九州歯科大学, 歯学部, 助教 (60468303)

Co-Investigator(Kenkyū-buntansha) 松原 琢磨  九州歯科大学, 歯学部, 准教授 (00423137)
川元 龍夫  九州歯科大学, 歯学部, 教授 (50323704)
佐藤 毅  埼玉医科大学, 医学部, 准教授 (60406494)
松尾 拡  九州歯科大学, 歯学部, 教授 (70238971)
郡司掛 香織  九州歯科大学, 歯学部, 助教 (90448811)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords骨芽細胞 / 骨形成 / Slitrk1 / 骨分化 / メカニカルストレス / 骨芽細胞活性化因子
Outline of Final Research Achievements

Slit and Trk-like protein 1 (Slitrk1) is associated with Tourette syndrome. Tourette patients exhibit delayed bone formation and increased bone fracture tendency. However, the role of Slitrk1 in bone homeostasis is completely unknown. We examined the role of Slitrk1 in osteoblastogenesis.
The expression levels of Slitrk1 increased with osteoblast differentiation in osteoblast lineage cells. Alkaline phosphatase (ALP) activity was decreased in BMSCs isolated from Slitrk1 null mice. In contrast, overexpression of Slitrk1 in C3H10T1/2 cells led to increased mRNA levels of ALP and osteocalcin induced by Runx2. BMP2-induced ectopic bone formed in Slitrk1 null mice was smaller than in wild-type littermates. Femoral bone volume of Slitrk1 null mice was decreased compared to control mice. These data suggest that Slitrk1 is expressed in osteoblasts where it enhances osteoblast differentiation.

Academic Significance and Societal Importance of the Research Achievements

本研究の研究成果により、矯正歯科治療時に生じる歯槽骨レベルの低下による保定時の後戻りや歯肉退縮等の歯科領域の問題解決のみならず、骨粗しょう症、変形性関節症などの運動器疾患の病態解明、新たな予防法や新規治療法の開発にも応用できる可能性がある。これまで骨粗しょう症に対する治療は骨吸収抑制薬の投与といった骨局所に対してアプローチを行う治療法が主流であったが、Slitrk1が神経分化と骨芽細胞分化を促進し、同時に促進することが解明されれば末梢の骨だけでなく中枢、すなわち脳も同時に活性化することが出来る新たな画期的な治療法に繋がる道も開かれ大いに期待できる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 2018

All Presentation (12 results) (of which Int'l Joint Research: 4 results)

  • [Presentation] Slitrk1, an integral membrane protein, promotes osteoblastogenesis2020

    • Author(s)
      Tomohiko Shirakawa, Takuma Matsubara, William N Addison, Kayoko N Kuroishi, Kaori Gunjigake, Tatsuo Kawamoto, Shoichiro Kokabu.
    • Organizer
      The 9th International Orthodontic Congress (9th IOC) )/第79回 日本矯正歯科学会学術大会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] トゥレット症候群原因遺伝子の1つSlitrk1は骨芽細胞分化を調整する2020

    • Author(s)
      白川智彦、松原琢磨、黒石加代子、郡司掛香織、川元龍夫、古株彰一郎
    • Organizer
      第15回九州矯正歯科学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Slitrk1, an integral membrane protein, regulates osteoblastogenesis2019

    • Author(s)
      Shirakawa T, Matsubara T, William N Addison, Urata M, Kuroishi K, Gunjigake K, Kawamoto T, Kokabu S
    • Organizer
      The 2nd Asian Symposium on Cutting-edge Biotechnology and Chemistry(2ndASCBC)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] トゥレット症候群原因遺伝子の1つSlitrk1は十分な骨芽細胞分化に必須である2019

    • Author(s)
      白川智彦、松原琢磨、黒石加代子、郡司掛香織、川元龍夫、古株彰一郎
    • Organizer
      第78回日本矯正歯科学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 膜タンパク質Slitrk1は骨芽細胞分化を促進する2019

    • Author(s)
      白川智彦、松原琢磨、William N Addison、黒石加代子、郡司掛香織、佐藤毅、川元龍夫、古株彰一郎
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Slitrk1, an integral membrane protein, controls osteoblast differentiation2019

    • Author(s)
      Shirakawa T, Matsubara T, William N Addison, Urata M, Kuroishi K, Gunjigake K, Sato T, Kawamoto T, Kokabu S
    • Organizer
      97th General Session & Exhibition of the International Association for Dental Research
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Slitrk1, an integral membrane protein, regulates osteoblast differentiation2019

    • Author(s)
      Shirakawa T, Matsubara T, William N Addison, Kuroishi K, Gunjigake K, Kokabu S, Kawamoto T
    • Organizer
      第7回アジア太平洋国際カンファレンス
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膜タンパク質であるSlitrk1は骨芽細胞分化を調整する2019

    • Author(s)
      白川智彦、松原琢磨、黒石加代子、郡司掛香織、川元龍夫、古株彰一郎
    • Organizer
      第79回九州歯科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] トゥレット症候群原因遺伝子の1つSlitrk1 は骨芽細胞分化に関与する2019

    • Author(s)
      白川智彦、古株彰一郎、松原琢磨、黒石加代子、郡司掛香織、川元龍夫
    • Organizer
      第14回九州矯正歯科学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Slitrk1, an integral membrane protein, controls osteoblast differentiation2019

    • Author(s)
      Tomohiko Shirakawa, Takuma Matsubara, William N Addison, Mariko Urata, Kayoko N Kuroishi, Kaori Gunjigake, Tsuyoshi Sato, Tatsuo Kawamoto, Shoichiro Kokabu
    • Organizer
      IADR/AADR/CADR General Session & Exhibition
    • Related Report
      2018 Research-status Report
  • [Presentation] 細胞膜貫通型タンパク質Sltrik1は骨芽細胞分化を促進する2018

    • Author(s)
      白川智彦、松原琢磨、中富千尋、黒石加代子、郡司掛香織、川元龍夫、佐藤毅、古株彰一郎
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] トゥレット症候群原因遺伝子の1つSlitrk1は骨芽細胞分化を促進する2018

    • Author(s)
      白川智彦、古株彰一郎、松原琢磨、黒石加代子、郡司掛香織、川元龍夫
    • Organizer
      第77回日本矯正歯科学会学術大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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