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Publication : Role of osteoprotegerin in arterial calcification: development of new animal model.

First Author  Orita Y Year  2007
Journal  Arterioscler Thromb Vasc Biol Volume  27
Issue  9 Pages  2058-64
PubMed ID  17615383 Mgi Jnum  J:134902
Mgi Id  MGI:3790028 Doi  10.1161/ATVBAHA.107.147868
Citation  Orita Y, et al. (2007) Role of osteoprotegerin in arterial calcification: development of new animal model. Arterioscler Thromb Vasc Biol 27(9):2058-64
abstractText  OBJECTIVES: 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. METHODS AND RESULTS: Male OPG (-/-), OPG (+/-), and OPG (+/+) mice were fed a high phosphate diet from 6 to 10 weeks after birth, and then 1alpha,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. CONCLUSIONS: 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.
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