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Impact of Microenvironmental Acidification via pH-Sensing Receptors on Bone Metabolism and Lifespan

Research Project

Project/Area Number 20K08879
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionGunma University

Principal Investigator

Mogi Chihiro  群馬大学, 生体調節研究所, 助教 (00375528)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordspH / Gタンパク質共役型受容体 / 骨代謝 / マウス / ターコイズキリフィッシュ
Outline of Research at the Start

骨量は骨芽細胞による骨形成と破骨細胞による骨吸収のバランスにより調節され、そのバランスはホルモンなど細胞外の要因から影響を受ける。細胞外の微小環境の酸性化を感知する受容体OGR1は骨芽細胞と破骨細胞に発現することから低pH環境のセンサーとして働くと考えられる。アシドーシスを誘導した時に酸性化がOGR1を介して骨代謝を調節する機構を個体レベルと器官培養を用いて細胞レベルで明らかにする。本研究は将来的に骨代謝環境の改善を通じて健康寿命の延伸に貢献できると考える。

Outline of Final Research Achievements

The bone mineral density is regulated by osteoclastic bone resorption and osteoblastic mineralization. It is well known that extracellular factors like hormones and cytokines alter osteoclast's and osteoblast's function, but it isn’t known how extracellular pH (the concentration of hydrogen ions) affect to the bone mineral metabolism. Proton-sensing G-protein coupled receptors including OGR1, GPR4, TDAG8, are expressed in bone cells. This study aimed to clarify how these pH receptors regulate the balance of bone resorption and mineralization and lifespan in whole-body level using mice and fish.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会において運動機能障害は現代の日本が抱える大きな問題である。その要因として加齢による骨密度の低下と筋肉の減少(サルコペニア)は解決すべき課題である。による局所的な炎症などを原因とした細胞外酸性化を感知するpH受容体と骨代謝の関係、また加齢により減少する筋肉に関する本研究の成果はこれらの問題の解決方法の基礎的な知見を提供するものである。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (11 results)

All 2024 2022 2020

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Sex-dependent regulation of vertebrate somatic growth and aging by germ cells2024

    • Author(s)
      Kota Abe, Hikaru Ino, Tomomi Niwa, Daniel Semmy, Ayami Takaochi, Takashi Nishimura, Chihiro Mogi, Maki Uenaka, Masaru Ishii, Kaori Tanaka, Yasuyuki Ohkawa, Tohru Ishitani
    • Journal Title

      Science Advances

      Volume: -

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid reverse genetics systems for Nothobranchius furzeri, a suitable model organism to study vertebrate aging2022

    • Author(s)
      Oginuma Masayuki、Nishida Moana、Ohmura-Adachi Tomomi、Abe Kota、Ogamino Shohei、Mogi Chihiro、Matsui Hideaki、Ishitani Tohru
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 11628-11628

    • DOI

      10.1038/s41598-022-15972-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis2022

    • Author(s)
      Haraoka Yukinari、Akieda Yuki、Nagai Yuri、Mogi Chihiro、Ishitani Tohru
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41467-022-29061-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The protective role of proton-sensing TDAG8 in the brain injury in a mouse ischemia reperfusion model.2020

    • Author(s)
      Sato K, Tobo A, Mogi C, Tobo M, Yamane N, Tosaka M, Tomura H, Im DS, Okajima F.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 17193-17193

    • DOI

      10.1038/s41598-020-74372-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Species-Dependent Enhancement of Ovarian Cancer G Protein-Coupled Receptor 1 Activation by Ogerin.2020

    • Author(s)
      Murakami S, Mochimaru Y, Musha S, Kojima R, Deai M, Mogi C, Sato K, Okajima F, Tomura H.
    • Journal Title

      Zoolog Sci.

      Volume: 37 Issue: 2 Pages: 103-108

    • DOI

      10.2108/zs190106

    • NAID

      210000171197

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A missense mutation of Leu74Pro of OGR1 found in familial amelogenesis imperfecta actually causes the loss of the pH-sensing mechanism.2020

    • Author(s)
      Sato K, Mogi C, Mighell AJ, Okajima F.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 526 Issue: 4 Pages: 920-926

    • DOI

      10.1016/j.bbrc.2020.04.005

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Involvement of GPR4 in increased <i>growth hormone</i> and <i>prolactin</i> expressions by extracellular acidification in MtT/S cells2020

    • Author(s)
      Musha S, Yoshida S, Murakami S, Kojima R, Deai M, Saso N, Mogi C, Sato K, Okajima F, Tomura H.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 66 Issue: 2 Pages: 175-180

    • DOI

      10.1262/jrd.2019-159

    • NAID

      130007830039

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ターコイズキリフィッシュ :新たな個体老化モデル2020

    • Author(s)
      阿部 耕太、小神野 翔平、茂木 千尋、荻沼 政之、前野 哲輝、石谷太
    • Journal Title

      月刊細胞

      Volume: 52 Pages: 23-26

    • Related Report
      2020 Research-status Report
  • [Presentation] 1.Effect of the pH-sensitive G protein-associated receptor OGR1 on the intestinal microbiota2020

    • Author(s)
      Hidekazu Ikeuchi, Maaya Awata, Chihiro Mogi, Takeshi Shimosato
    • Organizer
      International Union of Microbiological Societies 2020 Daejeon, Korea (IUMS 2020)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 2.エナメル質形成不全症の家系から発見されたプロトン感知性受容体OGR1変異体Leu74P2020

    • Author(s)
      佐藤幸市、茂木千尋、Alan J. Mighell、岡島史和
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Book] 動物の事典(末光隆志総編集)2020

    • Author(s)
      茂木千尋 (共著)
    • Total Pages
      772
    • Publisher
      朝倉書店
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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