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Organization of nuclear architecture and gene expression during osteoblast differentiation

Research Project

Project/Area Number 18K09047
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionTokyo Dental College

Principal Investigator

Nakamura Takashi  東京歯科大学, 歯学部, 講師 (80431948)

Co-Investigator(Kenkyū-buntansha) 小野寺 晶子  東京歯科大学, 歯学部, 講師 (90637662)
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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsRunx2 / アルカリホスファターゼ / 骨芽細胞分化 / 細胞核機能制御 / 骨芽細胞 / 転写制御 / 遺伝子発現制御
Outline of Final Research Achievements

Tissue-nonspecific alkaline phosphatase (TNAP) promotes hydroxyapatite crystal formation by degrading inorganic pyrophosphate (PPi) and increasing inorganic phosphate (Pi) concentration. However, abnormalities in Alpl KO mouse-derived osteoblasts are poorly understood. Therefore, in this study, we aimed to investigate the precise role of TNAP in osteoblast differentiation. TNAP inhibition by levamisole, a reversible TNAP inhibitor, suppressed the osteoblast differentiation. Alpl overexpression increased the expression of Runx2, Sp7, Bglap2 and Dmp1 in Alpl KO cells. TNAP regulated Runx2 expression, which in turn regulated the expression of all other osteoblast markers, except Dmp1. Dmp1 expression was independent of RUNX2 but was dependent on extracellular Pi concentration in Runx2-deficient osteogenic cells. These results suggest that TNAP functions as an osteogenic differenti- ation regulator either by regulating Runx2 expression or by controlling extracellular Pi concentration.

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会を迎えた我が国では骨粗鬆症などの骨疾患患者数の増加が問題となっており、これに対する新たな予防法・治療法の開発が求められている。本研究ではアルカリホスファターゼが骨形成を直接促進する因子である事が明らかとなったことから、アルカリホスファターゼを標的とした硬組織疾患に対する新規予防法・治療法の開発が期待できる。

Report

(2 results)
  • 2020 Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Sphenoid bone hypoplasia is a skeletal phenotype of cleidocranial dysplasia in a mouse model and patients2019

    • Author(s)
      Mitomo Keisuke、Matsunaga Satoru、Kitamura Kei、Nakamura Takashi、Saito Akiko、Komori Toshihisa、Muramatsu Takashi、Yamaguchi Akira
    • Journal Title

      Bone

      Volume: 120 Pages: 176-186

    • DOI

      10.1016/j.bone.2018.10.028

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2018-04-23   Modified: 2024-12-25  

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