| Project/Area Number |
15390552
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
KATSUBE Ken-ichi Tokyo Medical and Dental University, Graduate School of Medical and Dental Research, assistant professor, 大学院・医歯学総合研究科, 講師 (20233760)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Kei Tokyo Medical and Dental University, Graduate School of Medical and Dental Research, assistant, 大学院・医歯学総合研究科, 助手 (00302886)
NAKANISHI Toru Shujitsu University, Dept.Pharmacology, Professor, 薬学部, 教授 (30243463)
UMEZAWA Akihiro National Institute of Child Health and Development, Director, 部長 (70213486)
KUDO Akira Tokyo Institute of Technology, Graduate School of Life Sciences, Professor, 大学院・生命理工学研, 教授 (70178002)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | notch / CCN / stem cells / restitutive medicine / 硬組織 |
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| Research Abstract |
There will be more needs for the restitutive medicine of bone and dentine in near future and it is an important initial step to clarify their molecular basis. Particularly, establishment and development of the stem cells that are related to the bone or dentine formation is fundamental, but until now it was not easy to make the cell lines that have high potential of differentiation ability but without tumorigenesis. We focused on the CCN and Notch signal that are important for the stem cell regulation and applied them for a mesenchymal stem cell line that has osteogenic ability.
When the notch signal is constitutively activated in this cell line, the potential of osteogenesis is suppressed while neurogenic potential was upregulated. Global gene expression analysis using gene chip methods revealed that CCN3 (former name nephroblastoma overexpressed gene, Nov) dynamically changed its expression level corresponding to the notch signal. Then we constructed several truncated forms of the CCN3 to know its role in osteogenesis in this cell line. CCN3 was previously reported to express in a specific pattern during bone restitution and to associate with the exracellular domain of Notch protein to stimulate its signal. Several truncated forms greatly upregulated the osteogenesis, which indicates their dominant negative effects. We got several important progress in the osteogenic restitutive medicine indicating the possibility of the novel development of drugs.
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