| Project/Area Number |
18590814
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
YOSHIZUMI Masao Hiroshima University, Graduate School of Biomedical Sciences, Professor (20282626)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Hideya Hiroshima University, Hospital, Lecturer (70335678)
ISHIDA Takafumi Hiroshima University, Hospital, Lecturer (40346482)
OZONO Ryoji Hiroshima University, Hospital, Lecturer (00304436)
KAWAMATA Seiichi Hiroshima University, Graduate School of Health Sciences, Professor (30127641)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Arteriosclerosis / Vascular Calcification / Bone Metabolism-related Factors / Vascular Smooth Muscle Cells / Animal Model |
|---|
| Research Abstract |
Enhanced osteoclastogenesis, increased bone resorption, and osteoporosis have been reported in osteoprotegerin-deficient (OPG (-/-)) mice. OPG (-/-) mice available in Japan usually do not show vascular calcification. We have found that arterial calcification can be quickly induced by a simple procedure in OPG (-/-) mice.
Male OPG(-/-) OPG (+/-), and OPG (-/-) mice were fed a high phosphate diet from 6 to 10 weeks after birth, and then 1 ,25-dihydroxyvitamin D3 (calcitriol) was injected for 3 days. We found that severe calcification developed in the media of the aorta in OPG (-/-) mice. Under electron microscopy, calcium deposits were observed in the cytoplasm and extracellular matrix of vascular smooth muscle cells (VSMCs). Neither apoptosis of VSMCs nor infiltration of macrophages was observed. Alkaline phosphatase (ALP) activity of aortic tissue correlated with the calcified lesion area. Mouse aorta and bone extracts revealed an identical pattern by ALP electrophoresis.
Our results demonstrated that OPG had anticalcification activity in the aorta, probably through the downregulation of ALP activity. Because the time course of arterial calcification after the injection of calcitriol is accurate and reproducible, this mouse model will be useful for further investigation of vascular calcification.
|
