| Project/Area Number |
06454584
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
矯正・小児・社会系歯学
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| Research Institution | THE UNIVERSITY OF TOKUSHIMA |
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Principal Investigator |
HIURA Kenji (1995) TOKUSHIMA UNIVERSITY,SCHOOL OF DENTISTRY,ASSISTANT PROFESSOR, 歯学部・附属病院, 講師 (20228696)
河田 照茂 (1994) 徳島大学, 歯学部, 教授 (40029971)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Kahori TOKUSHIMA UNIVERSITY,SCHOOL OF DENTISTRY,RESEARCH ASSISTANT, 歯学部, 助手 (50274238)
KAMIOKA Hiroshi TOKUSHIMA UNIVERSITY,SCHOOL OF DENTISTRY,RESEARCH ASSISTANT, 歯学部, 助手 (80253219)
SUMITANI Koji TOKUSHIMA UNIVERSITY,SCHOOL OF DENTISTRY,ASSISTANT PROFESSOR, 歯学部・附属病院, 講師 (30206586)
日浦 賢治 徳島大学, 歯学部附属病院, 講師 (20228696)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | OSTEOCLAST / OSTEOCYTE / BONE MATRIX PROTEIN / C-SRC / TYROSINE PHOSPHORYLATION / CORTACTIN / CYTOSOLIC CALCIUM / EXTRA CELLULAR CALCIUM / pp60c-src / リン酸化 |
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| Research Abstract |
Osteoclasts are multinucleated cells derived from hematopoietic precursors that have the unique ability to excavate bone matrix. In cultured rat marrow cells with bone particles (100mug/cm^2 ; 20-53mum), osteoclast-like cell number and bone resorbing activity increased by 1.5- and 30-fold, respectively. Recent observations on mice engineered to have targeted knockout of the c-src gene resulted in a phenotype bearing a recessive form of osteopetrosis, a consequence of a decrease in osteoclast function. since osteoclasts were still present in the homozygous src-mutants, it was postulated that the defect could be with the osteoclast itself. Therefore, we have used Chicken osteoclasts as a model system to study of signal transduction. Activation of osteoclasts by bone particles results in elevated tyrosine phosphorylation of three proteins, p200, p130, and p85. By immunoprecipitation and western blotting technique, we demonstrated that p85 was identified with Cortactin. This tyrosine phosphoprotein is a previously characterized cytoskeletal substrate for c-src in transformed cells. The data suggested that Cortactin was one of the members for src dependent signal transduction in activated osteoclast.
Furthermore, we demonstrated that cytosolic calcium elevation that occurred in osteocytes on exposure to elevated extracellular calcium was independent of membrane voltage and was insensitive to modulation by organic calcium channel modulators, namely, BAY K 8644, nicardipine, and nifedipine. However, an intracellular calcium antagonist such as TMB-8 affected the cytosolic calcium level, suggesting that the cytosolic calcium elevation was due to mobilization of this cation from an intracellular store.
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