| Project/Area Number |
17H04368
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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 | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
阿部 真土 大阪大学, 歯学研究科, 講師 (40448105)
宇佐美 悠 大阪大学, 歯学研究科, 講師 (80444579)
保田 英洋 大阪大学, 工学研究科, 教授 (60210259)
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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 |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Keywords | Dmp1 / 骨細胞 / 翻訳後修飾 / リン酸化 / 石灰化 / 細胞内輸送 / Fam20C / 分泌経路 |
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| Outline of Final Research Achievements |
The bone matrix Dmp1 (dentin matrix protein 1), which is specifically produced by osteocytes, is cleaved into two fragments, N-terminal and C-terminal, during the post-translational modification. The C-terminal fragment is highly phosphorylated by kinase (Fam20C) and then localized at osteocyte canal wall, and will be involved in the osteocyte function. In this study, to investigate the role of Dmp1/C-terminal fragment, we studied the skeletal bone of transgenic mice (Fam20C-Tg) in which osteoblasts overexpress Fam20C. As a result, the highly phosphorylated Dmp1/C-fragment is involved in cortical bone formation due to elevated local mineralization. In addition, in vitro expression analysis of Dmp1 in which each N/C-fragments labeled with different colored-fluorescence suggested the intracellular transport pathways of both fragments were different after cleavage.
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| Academic Significance and Societal Importance of the Research Achievements |
骨に存在するDmp1等の酸性リン蛋白質は、多数のリン酸基が有する負電荷のため、Caイオンを引き寄せて骨形成に関与すると推測されていたが、これまで証明されていなかった。本研究では、生体でリン酸化したDmp1が石灰化を亢進して皮質骨形成に関与する事が示された。骨の全細胞の90%を占める骨細胞が特異的に発現するDmp1は、骨の形成・維持に深く関与すると考えられ、本結果は骨疾患の病態解明に繋がる有用な知見となる。
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