| Project/Area Number |
14571735
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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 | National Center for Geriatrics and Gerontology |
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Principal Investigator |
NIIDA Shumpei National Center for Geriatrics and Gerontology (NCGG), Institute for Longevity Sciences, Section Chief, 研究所・運動器疾患研究部, 室長 (10137630)
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| Co-Investigator(Kenkyū-buntansha) |
AMANO Hitoshi Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (90212571)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | flt-TK- / -mouse / op / op mouse / VEGF / CSF-1 / VEGFR-1 |
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| Research Abstract |
Bone development is coordinated with serial events such as matrix resorption, blood vessel invasion and marrow cavity formation with hematopoiesis. Colony-stimulating factor 1 (CSF-1) is the essential factor for differentiation, proliferation and survival of the macrophage lineage including osteoclasts. We have demonstrated that vascular endothelial growth factor (VEGF) can substitute for CSF-1 function in osteoclast formation through VEGF receptor-1 in CSF-1-deficient op/op mice. We introduced a VEGFR-1-signaling deficient mutation (flt-1 TK-/-) into the op/op mice. The double mutant (op/op flt-1 TK-/-) mice exhibited severe osteopetrosis and disorganization of growth plate. In addition, VEGF-dependent osteoclast formation could not recruit enough to generate marrow cavity in the op/op flt-1 TK-/-mice, and they showed severe osteomyelofibrosis. These results suggest that VEGFR-1 signal is predominant role for osteoclast formation in CSF-1-deficient condition and simultaneous signals from CSF-1 and VEGF are crucial for development and maintenance of bone marrow and cartilage structures.
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