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Elucidation of the role of Nopp140, a regulator of rRNA biosynthesis, in skeletal formation

Research Project

Project/Area Number 20K09891
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionNagasaki University

Principal Investigator

Matsuura Keiko  長崎大学, 医歯薬学総合研究科(歯学系), 特別研究員 (20770423)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsRunx2 / Nopp140 / 軟骨細胞 / 増殖 / 分化 / 軟骨増殖 / 軟骨分化 / BMPシグナル / 骨格形成
Outline of Research at the Start

本申請は、リボソーム生合成、細胞分裂や細胞増殖・分化、アポトーシス等様々な細胞動態を制御するセリン・ スレオニンキナーゼ casein kinase 2 (CK2)の抑制というこれまでに報告されているNopp140の機能をもとに、全く不明である骨・軟骨形成における機能を明らかにしていく。また、ノックアウトマウスおよびマイクロアレイ解析により、この2つ以外のNopp140の機能も明らかにできるように研究を立案した。

Outline of Final Research Achievements

Searching for Runx2 target genes in primary chondrocytes derived from Runx2-/- mice, we found that Runx2 up-regulated Nopp140 expression. In order to clarify the function of Nopp140 in chondrocytes, functional analysis was performed by generating chondrocyte-specific Nopp140 tg mice using the Co2a1 promoter, and it was thought that chondrocyte proliferation was reduced and hypertrophy was promoted. Therefore, in order to investigate the physiological functions of Nopp140, last year we succeeded in generating Nopp140 germline knockout mice and Nopp140 flox mice using the CRISPR/Cas9 system, and we conducted phenotypic analysis.

Academic Significance and Societal Importance of the Research Achievements

Nopp140は、骨・軟骨においては全く未知のタンパク質であり、その機能解明は独自性の極めて高い研究である。また、軟骨細胞・骨芽細胞の増殖・分化・アポトーシスの新たなシグナル経路の発見につながる独創性の高い研究である。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (2 results)

All 2020

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

  • [Journal Article] Expression of a Constitutively Active Form of Hck in Chondrocytes Activates Wnt and Hedgehog Signaling Pathways, and Induces Chondrocyte Proliferation in Mice2020

    • Author(s)
      Matsuura Viviane K. S. Kawata、Yoshida Carolina Andrea、Komori Hisato、Sakane Chiharu、Yamana Kei、Jiang Qing、Komori Toshihisa
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 8 Pages: 2682-2682

    • DOI

      10.3390/ijms21082682

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis2020

    • Author(s)
      Jiang Qing、Qin Xin、Yoshida Carolina Andrea、Komori Hisato、Yamana Kei、Ohba Shinsuke、Hojo Hironori、Croix Brad St.、Kawata-Matsuura Viviane K. S.、Komori Toshihisa
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 7 Pages: 2425-2425

    • DOI

      10.3390/ijms21072425

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2020-04-28   Modified: 2024-01-30  

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