| Project/Area Number |
11557139
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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 | 展開研究 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
TAKAHASHI Naoyuki School of Dentistry, Showa University Associate Professor, 歯学部, 助教授 (90119222)
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| Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Takenobu School of Dentistry, Showa University Lecturer, 歯学部, 講師 (80245802)
UDAGAWA Nobuyuki School of Dentistry, Showa University Lecturer, 歯学部, 講師 (70245801)
SHINKI Toshimasa School of Dentistry, Showa University Lecturer, 歯学部, 講師 (90138420)
TAKAMI Masamichi School of Dentistry, Showa University Assistant, 歯学部, 助手 (80307058)
須田 立雄 昭和大学, 歯学部, 教授 (90014034)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1999: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | Osteoclast / Osteoblast / Inflammatory cytokines / Calcium / BMP / RANKL / OPG / Osteoporosis / ODF / RANK / TNFα / IL-1 / 細胞内Ca |
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| Research Abstract |
Inhibition of signal transduction for osteoclastogenesis is thought to provide important information for development of anti-osteoporosis drugs. We have succeeded in molecular cloning of an essential factor for osteoclastogenesis, RANKL, which is expressed as a membrane associated factor in osteoblasts in response to many bone-resorbing factors. Using culture systems for osteoclast formation, we have studied signal transduction for osteoclastogenesis including RANK-RANKL signaling. The findings obtained from the study are as follows. (1) TNFα stimulated osteoclastogenesis in bone marrow-derived macrophage cultures in the presence of M-CSF.(2) SaOS-4/3, a subclone of the human osteosarcoma cell line SaOS-2, established by transfecting the human PTH/PTHrP receptor cDNA, supported osteoclast formation in response to PTH in co-culture with mouse bone marrow cells. Expression of mRNAs for RANKL and M-CSF by SaOS-4/3 cells was up-regulated in response to PTH.Both factors were expressed as membrane-associated factors. (3) Ionomycin and A23187 stimulated osteoclast formation in mouse co-cultures of bone marrow cells and osteoblasts. We also found that PMA, an activator of protein kinase C, stimulated osteoclast formation in the co-culture though up-regulation of RANKL expression in osteoblasts. (4) BMP-2 markedly enhanced osteoclast differentiation induced by RANKL and M-CSF.Addition of a soluble form of BMP receptor type-IA to the culture inhibited not only osteoclast formation induced by RANKL and BMP-2, but also the basal osteoclast formation supported by RANKL alone. Both bone marrow macrophages and mature osteoclasts expressed BMP-2 and BMP receptor type IA mRNAs. These findings provide important information for the development of anti-osteoporosis drugs.
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