The role of pH sensors in bone metabolism

• Project/Area Number: 17K09856
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Gunma University
• Principal Investigator: Mogi Chihiro 群馬大学, 生体調節研究所, 助教 (00375528)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: pH / Gタンパク質共役型受容体 / 骨芽細胞 / 破骨細胞 / 骨代謝

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 osteoclasts and osteoblasts functions. It seems that pH (the concentration of hydrogen ions) also play the important role in bone metabolism. Proton-sensing G-protein coupled receptors including OGR1, GPR4, TDAG8) are expressed in bone cells. We used differentiated osteoclasts and osteoblasts from pH-receptor bone marrow (BM) cells, and found some pH-receptors are expressed in BM cells and osteoclasts and osteoblasts. pH-receptors have the potential to modify the function or the differentiation of osteoblasts and osteoclast.

Academic Significance and Societal Importance of the Research Achievements

高齢化による運動機能障害は現代の日本が抱える大きな問題である。慢性疾患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について検討を行った本研究は、将来的には骨粗しょう症などの治療につながることが期待される。

Research Products

• [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
  • 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
  • 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
  • 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 cells (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of Molecular Mechanisms of Extracellular Acidification-Induced Intracellular Ca 2+ Increase in LβT2 Cells (2019)
  • Author(s): Kojima R, Horiguchi K, Mochimaru Y, Musha S, Murakami S, Deai M, Mogi C, Sato K, Okajima F, Tomura H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 517 Issue: 4 Pages: 636-641
  • DOI: 10.1016/j.bbrc.2019.07.083
  • Peer Reviewed
• [Journal Article] The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction. (2017)
  • Author(s): Nagasaka A, Mogi C, Ono H, Nishi T, Horii Y, Ohba Y, Sato K, Nakaya M, Okajima F, Kurose H.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 7812-7812
  • DOI: 10.1038/s41598-017-07573-2
  • Peer Reviewed / Open Access
• [Journal Article] Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR4 (2017)
  • Author(s): J. Negishi, Y. Omori, M. Shindo, H. Takanashi, S. Musha, S. Nagayama, J. Hirayama, H. Nishina, T. Nakakura, C. Mogi, K. Sato, F. Okajima, Y. Mochimaru, H. Tomura
  • Journal Title: J. Recept. Signal Transduct. Res. Volume: 37 Issue: 4 Pages: 401
  • DOI: 10.1080/10799893.2017.1298130
  • Peer Reviewed / Open Access
• [Presentation] 1.Effect of the pH-sensitive G protein-associated receptor OGR1 on the intestinal microbiota (2020)
  • Author(s): Hidekazu Ikeuchi1, Maaya Awata1, Chihiro Mogi2, Takeshi Shimosato3
  • Organizer: International Union of Microbiological Societies 2020 Daejeon, Korea (IUMS 2020), Fully Virtual Congress, 16(Mon)-20(Fri) November
  • 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Leu74P 口頭発表 (2020)
  • Author(s): 佐藤幸市1、茂木千尋1、Alan J. Mighell2、岡島史和3
  • Organizer: 第93回日本生化学会大会 一般演題（2020年9/14-16、パシフィコ横浜）
• [Presentation] T cell death associated gene 8 mediates MUC5AC expressions in the ovalbumin-induced asthma model. (2018)
  • Author(s): Hiroaki Tsurumaki, Haruka Saito-Aoki, Chihiro Mogi, Koichi Sato, Takashi Nakakura, Yasuhiko Koga, Masakiyo Yatomi, Makiko Sato, Kunio Dobashi, Fumikazu Okajima and Takeshi Hisada
  • Organizer: XXIV WORLD CONGRESS OF ASTHMA 2018
  • Int'l Joint Research
• [Book] 動物の事典 第4章 4.3 細胞の情報伝達，細胞相互作用 p162-165 (2020)
  • Author(s): 末光 隆志 ほか
  • Total Pages: 772
  • Publisher: 朝倉書店
  • ISBN: 9784254171662
• [Remarks] 群馬大学生体調節研究所シグナル伝達グループホームページ
  • URL: https://signal-transduction.imcr.gunma-u.ac.jp/