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Pharmacological Study on Neural Regulation of Bone Metabolism

Research Project

Project/Area Number 11671861
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionAichi-Gakuin University

Principal Investigator

TOGARI Akifumi  Aichi-Gakuin University, School of Dentistry, Department of Pharmacology, Professor, 歯学部, 教授 (80126325)

Co-Investigator(Kenkyū-buntansha) KONDO Ayami  Aichi-Gakuin University, School of Dentistry, Department of Pharmacology, Research Associate, 歯学部, 助手 (70301629)
MOGI Makio  Aichi-Gakuin University, School of Dentistry, Department of Pharmacology, Assistant Professor, 歯学部, 講師 (00174334)
ARAI Michitsugu  Aichi-Gakuin University, School of Dentistry, Department of Pharmacology, Assistant Professor, 歯学部, 講師 (20097538)
HIRUKAWA Koji  Aichi-Gakuin University, School of Dentistry, Department of Pharmacology, Research Associate, 歯学部, 助手 (60340147)
坪井 孝博  愛知学院大学, 歯学部, 講師 (00308777)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsOsteoblast / Osteoclast / Osteoclastogenesis / Sympathetic neurons / Axon guidance molecules / RANKL / OPG / β-受容体 / 骨吸収 / VIP / CGRP / エピネフリン / インターロイキン / ODF / ニューロトロフィン / セマフォリン / ネトリン
Research Abstract

In the present study, analysis of mRNA expression using RT-PCR demonstrated that human osteoblastic and osteoclastic cells are equipped with adrenergic receptors and neuropeptide receptors and constitutively express diffusible axon guidance molecules, suggesting that the extension of axons of sympathetic and peripheral sensory neurons to these cells is required for the dynamic neural regulation of local bone metabolism. Adrenergic stimulation was demonstrated to modulate the expression of IL-6, IL-11, cyclooxygenase-II, ODF/OPGL/TRANCE/RANKL(ODF/RANKL) and OCIF/OPG in osteoblasts/stromal cells. These molecules are well known to be involved in osteoclastogenesis. Especially, ODF/RANKL and OCIF/OPG are noticed as direct molecules modulating osteoclastogenesis. To elucidate the adrenergic regulation of osteoclastogenesis, we examined the effects of epinephrine (Epi), isoprenaline (Isp) and phenylephrine (Phe) on the formation of tartarate-resistant acid phosphatase(TRACP)-positive multinucleated cell (MNC) from mouse bone marrow cells. TRACP-positive MNC formation were stimulated by Isp or Epi, but not Phe. The MNC formation induced by Isp was not observed in the presence of OCIF/OPG, suggesting the importance of physiological balance between ODF/RANKL and OCIF/OPG productions for osteoclastogenesis. From these results, it may be suggested that the activity of sympathetic nerves has a significant effect on osteoclastogenesis by modulating ODF and OCIF expression in bone marrow cells.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Togari, A.: "Expression of mRNAs for axon guidance molecules, such as sernaphorin-III, netrins and neurotrophins, in human osteoblasts and osteoclasts"Brain Research. 878. 204-209 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kinpara, K.: "Osteoclast differentiation factor in human osteosarcoma cell line"Journal of Immunoassay. 21(4). 327-340 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mogi, M.: "Anti-apoptotic action of nerve growth factor in mouse osteoblastic cell line"Life Sciences. 67. 1197-1206 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Togari, A.: "Expression of mRNAs for neuropeptides receptors, adrenergic receptors, neurotrophins and semaphorin Ill in human osteoblasts and osteoclasts"Frontiers of the Mechanisms of Memory and Dementia. (elsevier). 163-164 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kondo, A.: "Signal transduction system for interleukin-6 and interleukin-11 synthesis stimulated by epinephrine in human osteoblasis and human osteogenic sarcoma cells"Biochemical Pharmacology. 61. 319-326 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi, T.: "Adrenergic stimulation of osteoclastegetiesis mediated by ODF expression in MC3T3-E1 osteoblast-like cells"Biochemical Pharmacology. 61. 579-586 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mogi, M., Kondo, A., Kinpara, K. and Togari, A.: "Anti-apoptotic action of nerve growth factor in mouse osteoblastic cell line."Life Sciences. 67. 1197-1206 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Togari, A., Mogi, M, Arai, M., Yamamoto, S. and Koshihara, Y.: "Expression of mRNAs for axon guidance molecules, such as semaphorin-III, netrins and neurotrophins, in human osteoblasts and osteoclasts."Brain Research. 878. 204-209 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kinpara. K., Mogi, M., Kuzushima, M. and Togari, A.: "Osteoclast differentiation factor in human osteosarcoma cell line."Journal of Immunoassay. 21 (4). 327-340 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Togari, A., Arai, M., Mogi, M., Kondo, A., Tsuboi,T., Takeuchi, T., Yamamoto, S. and Koshihara, Y.: "Expression of mRNAs for neuropeptides receptors, adrenergic receptors, neurotrophins and semaphorin III in human osteoblasts and osteoclasts."Frontiers of the Mechanisms of Memory and Dementia (Elsevier). 163-164 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kondo, A., Mogi, M., Koshihara, Y. and Togari, A.: "Signal transduction system for interleukin-6 and interleukin-11 synthesis stimulated by epinephrine in human osteoblasts and human osteogenic sarcoma cells."Biochemical Pharmacology. 61. 319-326 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi, T., Tsuboi, T., Arai, M. and Togari. A.: "Adrenergic stimulation of osteoclastogenesis mediated by ODF expression in MC3T3-E1 osteoblast-like cells."Biochemical Pharmacology. 61. 579-586 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Togari, A.: "Expression of mRNAs for axon guidance molecules, such as semaphorin-III, netrins and neurotrophins, in human osteoblasts and osteoclasts."Brain Research. 878. 204-209 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kinpara, K.: "Osteoclast differentiation factor in human osteosarcoma cell line."Journal of Immunoassay. 21(4). 327-340 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mogi, M.: "Anti-apoptotic action of nerve growth factor in mouse osteoblastic cell line."Life Sciences. 67. 1197-1206 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Togari, A.: "Expression of mRNAs for neuropeptides receptors, adrenergic receptors, neurotrophins and semaphorin III in human osteoblasts and osteoclasts."Frontiers of the Mechanisms of Memory and Dementia. (Elsevier). 163-164 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kondo, A.: "Signal transduction system for interleukin-6 and interleukin-11 synthesis stimulated by epinephrine in human osteoblasts and human osteogenic sarcoma cells."Biochemical Pharmacology. 61. 319-326 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeuchi, T.: "Adrenergic stimulation of osteoclastogenesis mediated by ODF expression in MC3T3-E1 osteoblast-like cells."Biochemical Pharmacology. 61. 579-586 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Togari,A., Mogi,M., Arai,M.,Yamamoto,S.and Koshihara,Y.: "Expression of mRNAs for axon guidance molecnles, such as semaphorin-III, netrins and neurotrophins, in human osteoblasts and osteoclasts."Brain Research. 878. 204-209 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinpara,K.,Mogi M.,Kuzushima,M.and Togari,A.: "Osteoclast differentiation factor in human osteosarcoma cell line."Journal of Immunoassay. 21(4). 327-340 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mogi,M.,Kondo,A.,Kinpara,K.and Togari,A.: "Anti-apoptotic action of nerve growth factor in mouse osteoblastic cell line."Life Sciences. 67. 1197-1206 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kondo,A.,Mogi,M.,Koshihara,Y.and Togari,A.: "Signal transduction system for interleukin-6 and interleukin-11 synthesis stimulated by epinephrine in human osteoblasts and human osteogenic sarcoma cells."Biochemical Pharmacology. 61. 319-326 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeuchi,T.,Tsuboi,T.,Arai,M.and Togari.A.: "Adrenergic stimulation of osteoclastogenesis mediated by ODF expression in MC3T3-E1 osteoblast-like cells."Biochemical Pharmacology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Togari,A.,Arai,M.,Mogi,M.,Kondo,A.,Tsuboi,T.,Takeuchi,T.,Yamamoto,S.and Koshihara,Y.: "Expression of mRNAs for neuropeptides receptors, adrenergic receptors, neurotrophins and semaphorin III in human osteoblasts and osteoclasts."Frontiers of the Mechanisms of Memory and Dementia. (Elsevier). 163-164 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 新井通次ら: "ヒト骨芽細胞および破骨細胞に存在するアドレナリン受容体とその生理的役割"日本薬理学雑誌. 114巻4号. 76P (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 竹内俊充、戸苅彰史: "マウス骨芽細胞におけるODF,OCIFmRNA発現のアドレナリン作動薬による促進効果"歯科基礎医学会雑誌. 41巻5号. 148 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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