| Project/Area Number |
03454436
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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 |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
ABE Etsuko Showa Univ., School of Dentistry Associate Professor, 歯学部, 助教授 (70119147)
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| Co-Investigator(Kenkyū-buntansha) |
CHENG He Jin Showa Univ., School of Dentistry Assistant, 歯学部, 助手 (10205049)
MIYAURA Chisato Showa Univ., School of Dentistry Associate Professor, 歯学部, 構師 (20138382)
SHINKI Toshimasa Showa Univ., School of Dentistry Associate Professor, 歯学部, 構師 (90138420)
SUDA Tatsuo Showa Univ., School of Dentistry Professor, 歯学部, 教授 (90014034)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | osteoclast / osteoblast / complement / C3 receptor / 1alpha,25(OH)_2D_3 / C3 / bone resorption / 1α,25(OH)_2D_3 / マウス補体第3成分 / 骨髄間質細胞 / 肝臓 / 116kD / ILー1 |
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| Research Abstract |
We found a 190 kDa protein produced by bone marrow-derived stromal cells (ST2) and primary osteoblastic cells in response to 1alpha,25(OH)_2D_3. The protein was purified and unequivocally identified as the third component of mouse complement (C3). It is well known that C3 protein in blood stream is derived preferentially from the liver. We therefore compared the regulatory mechanism of C3 protein and C3 gene expression by 1alpha,25(OH)_2D_3 in bone and liver. 1alpha,25(OH)_2D_3 greatly increased the C3 protein production and mRNA expression both dose- and time-dependently in primary osteoblastic cells. However, C3 production by hepatocytes occurred irrespective of the presence or absence of 1alpha,25-(OH)_2D_3. These results clearly indicate that 1alpha,25(OH)_2D_3 tissue-specifically regulates the synthesis of C3 in bone. Similar results were obtained in in vivo experiments using vitamin D-deficient mice. The mRNA level of C3 was undetectable in bone of vitamin D-deficient mice and became detectalbe as ealry as 24 h after 1alpha,25(OH)_2D_3 injection. In contrast, there was no significant difference in the expression of hepatic C3 mRNA between vitamin D-deficient and -supplemented mice.
Addition of antibodies of C3 and C3 receptors into mouse bone marrow cultures strikingly inhibited osteoclast formation induced by 1alpha,25(OH)_2D_3. The inhibitory effect of C3 antibody on osteoclast formation preferentially occurred when the antibody was added between days 3 and 4 (the commitment stage of osteoclast differentiation). These results suggest that the C3 produced by osteoblastic cells in response to 1alpha,25(OH)_2D_3 is somehow involved in osteoclast development, probably in the commitment of macrophage-like cells into preosteoclasts.
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