Signal transduction and functional analysis of TRPM7 in the regulatory mechanism of tooth mineralization
| Project/Area Number |
16H05509
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Fukuoka Dental College |
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Principal Investigator |
okabe koji 福岡歯科大学, 口腔歯学部, 教授 (80224046)
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| Co-Investigator(Kenkyū-buntansha) |
進 正史 福岡歯科大学, 口腔歯学部, 講師 (70549261)
岡本 富士雄 福岡歯科大学, 口腔歯学部, 講師 (60153938)
鍛治屋 浩 福岡歯科大学, 口腔歯学部, 講師 (80177378)
松下 正之 琉球大学, 医学(系)研究科(研究院), 教授 (30273965)
岡 暁子 福岡歯科大学, 口腔歯学部, 准教授 (60452778)
福島 秀文 東北大学, 歯学研究科, 准教授 (70412624)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Keywords | TRPM7 / エナメル芽細胞 / エナメル質形成 / ミネラル輸送 / キナーゼ / エナメル質石灰化 / 歯の石灰化 / 象牙芽細胞 / 歯の形成 |
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| Outline of Final Research Achievements |
Channel kinase TRPM7 is a unique bi-functional cation channel containing a protein kinase domain and highly expressed in teeth. Using ameloblast-specific TRPM7 conditional knock out (cKO) mice and TRPM7 kinase mutant (KR) mice, the function of mineral transport and kinase activity of TRPM7 in tooth formation was investigated. In KR mice, the channel function of TRPM7 in ameloblasts was normal, but the minor enamel defects with hypomineralization and decreased phosphorylation of BMP signal molecules were observed. On the other hand, cKO mice showed the severe enamel hypomineralization and abnormal ameloblast morphology together with suppression of
TRPM7 ion transport. Therefore, it was found that both TRPM7 ion transport and kinase activity contribute to enamel formation through modulation of ameloblast differentiation and cell morphology.
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| Academic Significance and Societal Importance of the Research Achievements |
歯の石灰化過程を担うミネラル輸送の分子同定や石灰化機構に関しては多くが不明であり解明すべき必須課題である。本研究の学術的意義は、生体において最もエナメル芽細胞に高発現するミネラル輸送体TRPM7に注目し、歯の細胞特異的な遺伝子改変マウスを用いて、これまで困難であった歯の石灰化調節の分子機構解明に取組む点である。これらの取組は、歯の形成異常を特徴とする病態機序を解く上でも重要であり、歯の再生研究の基盤形成や創薬開発に向けての展開への社会的貢献にもつながると考えられる。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] The SCFβ-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis.2017
Author(s)
Shimizu K, Fukushima H, Ogura K, Lien EC, Nihira NT, Zhang J, North BJ, Guo A, Nagashima K, Nakagawa T, Hoshikawa S, Watahiki A, Okabe K, Yamada A, Toker A, Asara JM, Fukumoto S, Nakayama KI, Nakayama K, Inuzuka H, Wei W.
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Journal Title
Sci Signal. doi: 10.1126/scisignal.aah4117.
Volume: 10
Issue: 460
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN couplex localization and promotes renal cancer progression2016
Author(s)
Nagashima, K., Fukushima, H., Shimizu, K., Hidaka, M., Hasumi, H., Ikebe, T., Fukumoto, S., Okabe, K., Inuzuka, H.
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Journal Title
Oncotarget
Volume: 8
Issue: 6
Pages: 9947-9960
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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