2004 Fiscal Year Final Research Report Summary
Mechanism of osteoblast differantiation by statins via stimulation of VEGF gene transcription
| Project/Area Number |
15591976
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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 | Ohu University |
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Principal Investigator |
HORIUCHI Noboru Ohu University, School of Dentistry, Professor, 歯学部, 教授 (00107294)
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| Co-Investigator(Kenkyū-buntansha) |
KAWANE Thtsuya Ohu University, School of Dentistiy, Lecturer, 歯学部, 講師 (00265208)
ABE Masatoshi Ohu University, School of Dentistiy, Lecturer, 歯学部, 講師 (10254872)
MATSUNUMA Ayako Ohu University, School of Dentistry, Research Assistant, 歯学部, 助手 (30296040)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Statins / MC3T3-E1 cells / Vascular endotherial growth factor (VEGF) / BMP-2 / prenylation / P13 kinase / Mineralization |
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| Research Abstract |
Statins such as simvastatin inhibit cholesterol synthesis. We investigated statin effects on vascular endothelial growth factor (VEGF) expression in osteoblastic cells. Simvastatin (10^<-6> M) time-dependently augmented VEGF mRNA expression in MC3T3-E1 cells. Transcriptional activation of a VEGF promoter - luciferase construct significantly increased by simvastatin administration. The results indicate that the stimulation of the VEGF gene by simvastatin is transcriptional in nature. Statins stimulate VEGF expression in osteoblasts via reduced protein prenylation and the P13K pathway, promoting osteoblastic differentiation. We investigated the in vivo effect of atorvastatin on bone mineral density (BMD) in ovariectomized (OVX) rats. The combination of atorvastatin (2 mg/kg) and 17β-estradiol (E_2) significantly enhanced the BMD of lumbar vertebrae (L2-L4) compared to that of either E_2 or atorvastatin alone. Concomitant injections of atorvastatin (2 mg/kg) with hPTH(1-34) at a low dose (1 rig/kg) significantly enhanced the BMD of lumbar vertebrae in OVX rats. These findings demonstrate that chronic administration of atorvastatin appears to modestly enhance the BMD of the lumbar vertebrae of OVX rats treated with submaximal doses of E_2 and hPTH( 1-34).
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