| Project/Area Number |
12671763
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 MED DENT UNIV., MOL.PATHOL., ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 講師 (20233760)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASHIMA Nobuyuki TOKYO MED DENT UNIV., PULP BIOLOGY SPECIAL INVESTIGATOR OF THE COE, 大学院・医歯学総合研究科, COE特任講師 (60272605)
UMEZAWA Akihiro NAT.INST.CHILD HEALTH DEV., REPROD.MED., DEAN, 生殖医療研究部, 部長 (70213486)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | OSTEOGENESIS / STEM CELLS / NOTCH / Kusa / Micrarray / MEF2 / KUSA / 骨芽細胞 / gene array |
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| Research Abstract |
Notch signal is findamental for the growth and differentiation of stem cells, but its molecular mechanism is not yet fully understood. Particularly, it is difficult to know how the expression of ligand and receptor influences on the bimodal differentiation of stem cells. We have proven that Notch reoeptor can bind to its ligand in the same cell in a cell-autonomous manner, which plays an important part in this bimodal differentiation This property seems common and important for Notch signal not only in the hard tissue formation but also in other types of differentiation such as neuorogenesis or endothelial cell differentiation.
Kusa is a mouse bone marrow-derived mesenchymal stem cell line that has not only a strong osteogenic property but has a neurogenic potential that is inducible in a specific condition. To investigate the special differentiation ability of Kusa, we analyzed the gene expression pattern of Kusa using the microarray analyses. We applied the two different kinds of micr
… More
oarray for this analysis. As a result, we found that the vast range of downregulation occurred in the gene expression during osteogenesis. This result indicates that the osteogenic differentiation of Kusa may be triggered by the suppression of the genes not related to the osteogenesis, This is completely an opposite concept to the "master gene theory" though it is vely attractive. We also found that some genes related to the osteogenesis are upregulated by these screenings.
We examined the gene expression of Notch signal genes and found that the HES1, a downstream of Notch signal was transiently upregulated and this upregulation dynamically affected to other Notch signal genes. Based on this result, we constructed the stable Kusa transformant with the Notch constitutively active form (NICD). The NICD remarkably suppresses the osteogenic ability of Kusa both in vitro and in vivo. Kusa could form the small calcified nodules in the condition of NICD, which did not exhibit the mature osseous structure. However, NICD could inversely stimulate the neurogenic potential of Kusa. Actually, we are investigating how the Notch signal modifies the differentiation ability of Kusa, focusing on a member of CCN gene family, Nov (CCN3) that can interact with notch receptor. Less
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