Project/Area Number |
16K11827
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Periodontology
|
Research Institution | Niigata University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
多部田 康一 新潟大学, 医歯学系, 教授 (20401763)
|
Research Collaborator |
Yamazaki Kazuhisa
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
Keywords | 歯周炎 / 神経ペプチド / TRPチャネル / TRPV1 / 破骨細胞 / 実験的歯周炎モデルマウス / 破骨細胞分化 / 歯周病 |
Outline of Final Research Achievements |
However the function of TRPV1 in sensory neurons has been intensively studied in other organs, its physiological role in periodontal tissues is unclear. In this study, we found that Trpv1-/- mice developed severe bone loss in an experimental model of periodontitis. Chemical ablation of TRPV1-expressing sensory neurons recapitulated the phenotype of Trpv1-/- mice, suggesting a functional link between neuronal TRPV1 signaling and periodontal bone loss. TRPV1 activation in gingival nerves induced production of the neuropeptide, calcitonin generelated peptide (CGRP), and CGRP treatment inhibited osteoclastogenesis in vitro. Oral administration of the TRPV1 agonist, capsaicin, suppressed ligature-induced bone loss in mice with fewer tartrateresistant acid phosphatase (TRAP)-positive cells in alveolar bone. These results suggest that neuronal TRPV1 signaling in periodontal tissue is crucial for the regulation of osteoclastogenesis via the neuropeptide CGRP.
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Academic Significance and Societal Importance of the Research Achievements |
口腔領域には様々なTRPチャネルタンパクが発現していることが報告されていることから,歯周炎のみならず様々な口腔生理機能や口腔疾患の理解を深めるという学術的意義を持つと考える.さらに,TRPチャネルタンパクの歯周組織における役割が明らかになれば,将来的にはこれらのアゴニストもしくはアンタゴニストを歯周病の予防薬や治療薬として歯磨剤や含嗽剤として応用することが可能である.TRPチャネルタンパクのアゴニストはカプサイシンやメントールなど,自然界に存在しているものが多く,生体親和性が高いために臨床応用しやすく,トランスレーショナルリサーチ実践の即戦力と成り得ることが社会的意義として考えられる.
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