| Project/Area Number |
17H04366
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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 |
Morphological basic dentistry
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
下村 淳子 日本歯科大学, 新潟生命歯学部, 准教授 (00386286)
山本 格 新潟大学, 医歯学総合研究科, 特任教授 (30092737)
依田 浩子 新潟大学, 医歯学系, 准教授 (60293213)
大津 圭史 岩手医科大学, 歯学部, 准教授 (60509066)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
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| Keywords | 歯学 / プロテオーム / 発生・分化 / 細胞・組織 / 歯髄幹細胞 / 歯髄 / 長期ラベル細胞 / 静的幹細胞 / TetOP-H2B-GFPマウス / 前駆細胞 / 幹細胞ニッチ |
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| Outline of Final Research Achievements |
Analysis using TetOP-H2B-GFP mice demonstrated that quiescent stem/progenitor cells resided in the subodontoblastic layer in addition to the perivascular niche in the center of pulp tissue and that the domain of insulin-like growth factor binding protein 5 (IGFBP5) expression was overlapped with this niche. During 3-7 days after autograft, IGFBP5-positve cells were maintained in the dental pulp and lacked a TUNEL-positive reaction, suggesting that IGFBP5 plays a pivotal role in regulating the survival and apoptosis of dental pulp stem cells during both tooth development and pulpal healing following tooth injury. Proteome analysis showed that 156 odontoblast, 183 subodontoblastic, and 76 central pulp tissue layers -specific proteins were identified in molars and that these layers shared 76-988 proteins. The apical bud epithelium and subjacent mesenchyme possessed 258 and 318 tissue-specific proteins, respectively, and shared 1350 proteins in continuously growing incisors.
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| Academic Significance and Societal Importance of the Research Achievements |
通常の状態では、歯髄ではめったに自己複製が起こらないので、歯髄には静的幹細胞が存在し、外的侵襲後に幹細胞が活性化状態になると考えられる。本研究により、歯髄幹細胞ニッチの維持におけるIGFBP5の役割、象牙芽細胞下層細胞におけるNestinタンパクの役割、幹細胞の増殖制御における微小環境の酸素の役割などを解明した。歯の発生過程および外的侵襲後の歯髄治癒過程における幹細胞を含む細胞群・シグナル分子・細胞外マトリックス相互作用の解明が歯の再生研究の進展の鍵を握っており、生体における細胞間相互作用を考える上で、遺伝子発現だけでなく、時空間的なタンパク質の変化を捉えることが、生物現象解明には必要である。
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