| Project/Area Number |
10671711
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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 | Meikai University |
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Principal Investigator |
HANEDA Yoshiyuki Meikai Uni. Sch.Dentistry, Associate Professor, 歯学部, 助教授 (90164772)
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| Co-Investigator(Kenkyū-buntansha) |
KUMEGAWA Masayoshi Meikai Uni. Sch.Dentistry, Professor, 歯学部, 教授 (40049367)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Osteoclasts / Bone resorption / Bone marrow cells / Gas6 / Tyro3 / c-src / FAK / PI3-kinase / Tyro-3 / トランスフェクション / Quantitative RT-PCR / Tyrosine phosphorylation |
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| Research Abstract |
Bone is continuously being formed and resorbed. This process is accomplished by the precise coordination of two cell types: osteoblasts and osteoclasts. Osteoclasts are large, multinucleated cells that are derived from the same hematopoietic precursors as macrophages. However, these bone-resorbing cells are difficult to study directly because of their relative inaccessibility. The purification of primary osteoclasts from rabbit bones by their adherent nature provides an opportunity for investigating the molecules in osteoclasts. We have examined the expression of receptor tyrosine kinases by PCR and found that Tyro-3 was frequently cloned from primary osteoclasts in PCR cloning. Immunohistochemistry revealed that Tyro-3 was expressed on the multinucleated osteoclasts which were positive for tartrate-resistant acid phosphatase (TRAP), but not on mononuclear TRAP-positive cells. The Tyro-3 ligand, Gas6 induced the phosphorylation of Tyro-3 receptors in osteoclasts in 5-10 mm Gas6 and protein S directly enhanced the bone-resorbing activity of mature osteoclasts. However, Gas6 did not affect the differentiation of osteoclasts from bone marrow cells. Gas6 and protein S are dependent on vitamin K, a cofactor for the enzyme responsible for carboxylation of glutamic acid residues. The findings in this study are the first to indicate a new biological activity of Gas6 and protein S as a direct regulator of osteoclastic function and give an insight into the role of these vitamin K-dependent ligands are involved in bone resorption in vivo.
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