2005 Fiscal Year Final Research Report Summary
Enhancement of BMP activity in vivo by heparin and analysis of its molecular mechanisms.
| Project/Area Number |
16591866
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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 |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
KAMIJO Ryutaro Showa University, School of Dentistry, Professor, 歯学部, 教授 (70233939)
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| Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Takenobu Saitama Medical School, School of Medicine, Associate Professor, 医学部, 助教授 (80245802)
MIYAMOTO Yoichi Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (20295132)
TAKAMI Masamichi Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (80307058)
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| Project Period (FY) |
2004 – 2005
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| Keywords | heparin / BMP / ectopic bone formation / noggin / samd1 / 5 / 8 / phosphorylation / C2C12 cells |
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| Research Abstract |
Although bone morphogenetic proteins (BMPs) are clinically useful for bone regeneration, large amounts of them are required to induce new bone formation in monkeys and humans. We recently found that heparin stimulated BMP activity in vitro. In the present study, we examined whether heparin can enhance the bone formation induced by BMPs in vivo and attempted to determine the molecular mechanisms by which heparin stimulates BMP activity using C2C12 myoblasts. Heparin enhanced BMP-2-induced gene expression and Smad1/5/8 phosphorylation at 24 hours and thereafter, though not within 12 hours. Heparitinase treatment did not affect the response of cells to BMP-2. The half-life of BMP-2 in culture media was prolonged more that 10-fold in the presence of heparin. Although noggin mRNA was induced by BMP-2 within 1 hour regardless of the presence of heparin, noggin failed to inhibit BMP-2 activity in the presence of heparin. Furthermore, simultaneous administration of BMP-2 and heparin in vivo dose-dependently induced larger amounts of mineralized bone tissue than BMP-2 alone. These findings clearly indicate that heparin enhances BMP-induced osteoblast differentiation not only in vitro but also in vivo. They also suggest that heparin protects BMPs from the inhibitory microenvironment around target cells.
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