Bone metabolism and its disruption in pH receptor knockout mice

• Project/Area Number: 24591349
• 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): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: pH / Gタンパク質共役型受容体 / 破骨細胞 / 骨芽細胞 / 関節炎

Outline of Final Research Achievements

It is well known that extracellular pH plays important roles in bone metabolism, but the molecular mechanisms are yet unidentified. To reveal the roles of novel four proton-sensing receptors (OGR1, GPR4, TDAG8, G2A) in bone remodeling, we generated osteoclasts and osteoblasts from bone marrow cells from pH-receptor knockout mice. These results indicate the relationship between OGR1 family and bone metabolism. We also assessed rheumatoid arthritis as in vivo model for studying acidification by accumulation of inflammatory cells.

Research Products

• [Journal Article] Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment. (2016)
  • Author(s): Ichijo Y, Mochimaru Y, Azuma M, Satou K, Negishi J, Nakakura T, Oshima N, Mogi C, Sato K, Matsuda K, Okajima F, Tomura H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 469 Pages: 81-6
  • Acknowledgement Compliant
• [Journal Article] Protective role of proton-sensing TDAG8 in lipopolysaccharide-induced acute lung injury. (2015)
  • Author(s): H. Tsurumaki, C. Mogi, H. Aoki-Saito, M. Tobo, Y. Kamide, M. Yatomi, K. Sato, K. Dobashi, T. Ishizuka, T. Hisada, M. Yamada, F. Okajima
  • Journal Title: Int. J. Mol. Sci. Volume: 16 Issue: 12 Pages: 28931-28942
  • DOI: 10.3390/ijms161226145
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells (2015)
  • Author(s): Y. Kamide, T. Ishizuka, M. Tobo, H. Tsurumaki, H. Aoki, C. Mogi, T. Nakakura, M. Yatomi, A. Ono, Y. Koga, K. Sato, T. Hisada, K. Dobashi, M. Yamada, F. Okajima
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 464 Issue: 3 Pages: 949
  • DOI: 10.1016/j.bbrc.2015.07.077
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of imidazopyridine compounds as negative allosteric modulators of proton-sensing GPR4 in extracellular acidification-induced responses (2015)
  • Author(s): Ayaka Tobo, Masayuki Tobo, Takashi Nakakura, Masashi Ebara, Hideaki Tomura, Chihiro Mogi, Dong-Soon Im, Naoya Murata, Atsushi Kuwabara, Saki Ito, Hayato Fukuda, Mitsuhiro Arisawa, Satoshi Shuto, Michio Nakaya, Hitoshi Kurose, Koichi Sato, Fumikazu Okajima
  • Journal Title: PLoS One. Volume: 10 Issue: 6 Pages: e0129334-e0129334
  • DOI: 10.1371/journal.pone.0129334
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish (2015)
  • Author(s): Y. Mochimaru, M. Azuma, N. Oshima, Y. Ichijo, K. Satou, K. Matsuda, Y. Asaoka, H. Nishina, T. Nakakura, C. Mogi, K. Sato, F. Okajima, H. Tomura
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 457 Issue: 4 Pages: 493
  • DOI: 10.1016/j.bbrc.2014.12.105
  • Peer Reviewed
• [Journal Article] Acidic pH increases cGMP accumulation through the OGR1/phospholipase C/Ca2+/neuronal NOS pathway in N1E-115 neuronal cells. (2014)
  • Author(s): M. Kotake, K. Sato, C. Mogi, M. Tobo, H. Aoki, T. Ishizuka, N. Sunaga, H. Imai, K. Kaira, T. Hisada, M. Yamada, F. Okajima
  • Journal Title: Cell. Signal. Volume: 26 Issue: 11 Pages: 2326-2332
  • DOI: 10.1016/j.cellsig.2014.07.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ionotropic and metabotropic proton-sensing receptors involved in airway inflammation in allergic asthma. (2014)
  • Author(s): Aoki H, Mogi C, Okajima F.
  • Journal Title: Mediators Inflamm. Volume: 712962 Pages: 712962-712962
  • DOI: 10.1155/2014/712962
  • Peer Reviewed / Open Access
• [Journal Article] Lipoprotein-associated lysolipids are differentially involved in high-density lipoprotein- and its oxidized form-induced neurite remodeling in PC12 cells. (2014)
  • Author(s): Koichi Sato, Masayuki Tobo, Chihiro Mogi, Naoya Murata, Mie Kotake, Atsushi Kuwabara, Dong-Soon Im, Fumikazu Okajima
  • Journal Title: Neurochemistry International Volume: 68 Pages: 38-47
  • DOI: 10.1016/j.neuint.2014.02.005
  • Peer Reviewed
• [Journal Article] Inhibition of interleukin-1β production by extracellular acidification through the TDAG8/cAMP pathway in mouse microglia. (2014)
  • Author(s): Ye Jin, Koichi Sato, Ayaka Tobo, Chihiro Mogi, Masayuki Tobo, Naoya Murata, Satoshi Ishii, Dong-Soon Im and Fumikazu Okajima
  • Journal Title: Journal of Neurochemistry Volume: 129(4) Issue: 4 Pages: 683-695
  • DOI: 10.1111/jnc.12661
  • Peer Reviewed / Open Access
• [Journal Article] Role of extracellular proton-sensing OGR1 in regulation of insulin secretion and pancreatic β-cell functions. (2014)
  • Author(s): Mogi C, Nakakura T, Okajima F.
  • Journal Title: Endocr J. Volume: 61 Pages: 101-110
  • NAID: 130004718264
  • Peer Reviewed
• [Journal Article] Proton-sensing ovarian cancer G protein-coupled receptor 1 on dendritic cells is required for airway responses in a murine asthma model (2013)
  • Author(s): Aoki H, Mogi C, Hisada T, Kamide Y, Ichimonji I, Tomura H, Tobo M, Sato K, Tsurumaki H, Dobashi K, Mori T, Harada H, Yamada M, Mori M, Ishizuka T, Okajima F
  • Journal Title: PLoS ONE Volume: 8 Issue: 11 Pages: e79985-e79985
  • DOI: 10.1371/journal.pone.0079985
  • Peer Reviewed
• [Journal Article] Deficiency of proton-sensing ovarian cancer G protein-coupled receptor 1 attenuates glucose- stimulated insulin secretion (2012)
  • Author(s): Nakakura T
  • Journal Title: Endocrinology Volume: 153 Issue: 9 Pages: 4171
  • DOI: 10.1210/en.2012-1164
  • Peer Reviewed
• [Presentation] pH受容体OGR1ファミリーの骨リモデリングにおける役割 (2013)
  • Author(s): 茂木 千尋、戸村 秀明、佐藤 幸市、岡島 史和
  • Organizer: 第12回生命科学研究会
  • Place of Presentation: 青森
• [Remarks] シグナル伝達グループ
  • URL: http://signal-transduction.imcr.gunma-u.ac.jp/
• [Remarks] 群馬大学生体調節研究所 シグナル伝達分野
  • URL: http://signal-transduction.imcr.gunma-u.ac.jp/
• [Remarks] 群馬大学生体調節研究所シグナル伝達分野
  • URL: http://www.imcr.gunma-u.ac.jp/lab/sigtra/
• [Remarks] 生体調節研究所・シグナル伝達分野
  • URL: http://www.imcr.gunma-u.ac.jp/lab/sigtra/