| Project/Area Number |
11470393
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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 |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
UDAGAWA Nobuyuki School of Dentistry, Showa University Lecturer, 歯学部, 講師 (70245801)
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| Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Jakenobu School of Dentistry, Showa University Lecturer, 歯学部, 講師 (80245802)
SHINKI Toshimasa School of Dentistry, Showa University Lecturer, 歯学部, 講師 (90138420)
TAKAHASHI Naoyuki School of Dentistry, Showa University Associate Professor, 歯学部, 助教授 (90119222)
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 |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | Osteoclast / Bone resorption / Osteoblast / RANKL / OPG / TNF / 1α, 25(OH)_2D_3 / PTH / 骨随間質細胞 / マクロファジーコロニー刺激因子 |
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| Research Abstract |
Osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-κB ligand (RANKL)/osteoclast differentiation factor (ODF), inhibits both differentiation and function of osteoclasts. We previously reported that OPG-deficient mice exhibited severe osteoporosis caused by enhanced osteoclastic bone resorption. In the present study, potential roles of OPG in osteoclast differentiation were examined using a mouse co-culture system of calvarial osteoblasts and bone marrow cells prepared from OPG-deficient mice. In the absence of bone-resorbing factors, no osteoclasts were formed in co-cultures of wild-type (+/+) or heterozygous (+/-) mouse-derived osteoblasts with bone marrow cells prepared from homozygous (-/-) mice. In contrast, homozygous (-/-) mouse-derived osteoblasts strongly supported osteoclast formation in the co-cultures with homozygous (-/-) bone marrow cells even in the absence of bone-resorbing factors. Addition of OPG to the co-cultures with osteoblasts
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and bone marrow cells derived from homozygous (-/-) mice completely inhibited spontaneously occurring osteoclast formation. Adding 1α, 25-dihydroxyvitamin D3 [1α, 25(OH)2D3] to these co-cultures significantly enhanced osteoclast differentiation. In addition, bone-resorbing activity in organ cultures of fetal long bones derived from homozygous (-/-) mice was markedly increased irrespective of the presence and absence of bone-resorbing factors in comparison with that from wild-type (+/+) mice. Osteoblasts prepared from homozygous (-/-), heterozygous (+/-) and wild-type (+/+) mice constitutively expressed similar levels of RANKL mRNA, which were equally increased by the treatment with 1α, 25(OH)2D3. When homozygous (-/-) mouse-derived osteoblasts and hemopoietic cells were co-cultured, but direct contact between them was prevented, no osteoclasts were formed even in the presence of 1α, 25(OH)2D3 and M-CSF.These findings suggest that OPG produced by osteoblasts/stromal cells is a physiologically important regulator in osteoclast differentiation and function, and that RANKL expressed by osteoblasts functions as a membrane-associated form. Less
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