| Project/Area Number |
16390543
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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 |
Conservative dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KAWASHIMA Nobuyuki Tokyo Medical and Dental University Graduate School, Department of Restorative Sciences, Associate Professor, 大学院医歯学総合研究科, COE特任助教授 (60272605)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Kei Tokyo Medical and Dental University Graduate School, Department of Oral Restitution, Research Associates, 大学院医歯学総合研究科, 助手 (00302886)
KATSUBE Ken-ichi Tokyo Medical and Dental University Graduate School, Department of Oral Restitution, Lecturer, 大学院医歯学総合研究科, 講師 (20233760)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Keywords | osteoblasts / Notch / Nov / mesenchymal cells / differentiation / mineralization / CBF1 / RBP-Jκ / Kusa-A1 / 硬組織形成 / 骨髄ストローマ細胞 / KusaA1 / 骨髄ストローマ |
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| Research Abstract |
Notch is a transmembrane receptor that plays a crucial role in differentiation of stem cells. Its role in the formation of mesenchymal tissues has also been implicated although detailed mechanism has not yet been analyzed. To elucidate the function of Notch signaling in osteogenesis, we transfected the constitutively active Notch 1 (Notch intracellular domain, NICD) into two different osteoblastic mesenchymal cell lines, Kusa-A1 and KusaO, and established stable transformants (KusaA1NICD and KusaONICD) to examine the Notch signaling. NICD generally suppressed the expression of osteogenic marker genes, calcium deposition and in vitro mineralization in both Kusa-A1 and KusaO. The promoter activities of the Cbfa1 and the Ose2 element were attenuated by NICD. In vivo bone formation of Kusa-A1 was significantly suppressed by NICD. These results suggest that Notch signaling functions as a general coordinator of osteogenesis through cell-cell interactions.
Nephroblastoma overexpressed gene (Nov : CCN3) is a cysteine-rich protein that is overexpressed in avian nephroblastomas, and it is thought to be involved in the control of cell proliferation and development of various tissues. As Nov has recently reported to bind Notch, we evaluated the Nov signaling in the osteoblastic mesenchymal cell lines. Transfection of Nov expression vector to Kusa-A1 induced downregulation of osteoblastic markers. On the centrally, Notch related genes were upregulated. DNA microarray revealed that Nov expression was highly induced in KusaA1NICD. Therefore, Nov may induce the Notch signaling, which further induced Nov expression, and this cycle may be essential to keep the cells in immature condition.
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