| Project/Area Number |
17591956
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
TOGARI Akifumi Aichi Gakuin University, School of Dentistry Department of Pharmacology, Professor (80126325)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Michitsugu Aichi-Gakuin University, School of Dentistry Department of Pharmacology, Assistant Professor (20097538)
OBATA Koji Aichi-Gakuin University, School of Dentistry Department of Pharmacology, Assistant Professor (40378229)
HIRUKAWA Koji Aichi-Gakuin University, School of Dentistry Department of Pharmacology, Assistant Professor (60340147)
茂木 眞希雄 愛知学院大学, 歯学部, 講師 (00174334)
森田 あや美 愛知学院大学, 歯学部, 助手 (70301629)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,680,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Osteoblast / Nerve / Co-culture / Calcium ion / Scorpion venom / Synapse / 神経細胞 / 細胞内カルシウム / 骨代謝 / 交感神経 / 感覚神経 / イソプレナリン / 破骨細胞 / CGRP / RANKL / RAW264.7 / フォルスコリン / ヒト骨芽細胞 / cAMP / PKA / p-ERK / calphostin C |
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| Research Abstract |
The vertebrate skeleton is richly innervated with adrenergic and peptidergic nerve terminals, and these play important roles in bone remodelling. Recently showed that increased sympathetic nervous activity causes bone loss via an increase in bone resorption and a decrease in bone formation. Increased bone resorption is based on the stimulation of both osteoclast formation and osteoclast activity. And we also demonstrated that human osteoblastic as well as osteoclastic cells are equipped with adrenergic receptors (Ars) and neuropeptide receptors and that they constitutively express diffusible axon guidance molecules known to function as a chemoattractant and/or chemorepellent for growing nerve fibers. These findings suggest that the extension of axons of sympathetic and peripheral sensory neurons to osteoblastic and osteoclastic cells is required for the dynamic neural regulation of local bone metabolism. However, while several studies have shown a functional nerve-bone cell interplay,
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whether both osteoblastic and osteoclastic cells activation occurs as a direct response to neuronal activation or requires an intermediary cell is unclear. Therefore, we examined direct nerve-osteoblastic cell communication by using an in vitro co-culture model comprising mouse osteoblastic cells, MC3T3-El, and neurite-spouting mouse superior cervical ganglia. Following loading with the calcium fluorophore Fluo-3, neurite-osteoblastic cell units were examined by confocal laser scanning microscopy. The addition of scorpion venom (SV) elicited neurite activation (i.e., Ca^<2+> mobilization) and, after a lag period, osteoblastic Ca^<2+> mobilization. The SV had no direct effect on the MC3T3-El cells in the absence of neurites. The addition of an α1-AR antagonist, prazosin concentration-dependently prevented the osteoblastic activation that resulted as a consequence of the neural activation by SV. Thus, our recent findings demonstrate that MC3T3-E1 activation, as judge by Ca^<2+> mobilization, can be a direct consequence of contact with a specific activated nerve fiber. This evidence obtained in vitro demonstrates that nerve-osteoblastic cell cross-talk can occur in the absence of an intermediary transducing cell and that noradrenaline is an important mediator of this communication. Several recent in vivo and in vitro studies have demonstrated a sympathomimetic action on bone formation and resorption via osteoblastic and osteoclastic cells, respectively, expressing α-and β-Ars. Less
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