Role of Osteoprotegerin in Arterial Calcification
- 1 September 2007
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 27 (9), 2058-2064
- https://doi.org/10.1161/atvbaha.107.147868
Abstract
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 1α,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.Keywords
This publication has 33 references indexed in Scilit:
- Regulation of Vascular CalcificationCirculation Research, 2005
- Human Vascular Smooth Muscle Cells Undergo Vesicle-Mediated Calcification in Response to Changes in Extracellular Calcium and Phosphate ConcentrationsJournal of the American Society of Nephrology, 2004
- 1α,25 Dihydroxyvitamin D3 Rapidly Regulates the Mouse Osteoprotegerin Gene Through Dual PathwaysJournal of Bone and Mineral Research, 2004
- Induction of Bone-Type Alkaline Phosphatase in Human Vascular Smooth Muscle CellsCirculation Research, 2002
- Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and ActivationCell, 1998
- Identification of Arterial and Venous Segments of Blood Vessels Using Alkaline Phosphatase Staining of Ink/Gelatin Injected Tissues.Archives of Histology and Cytology, 1998
- Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA proteinNature, 1997
- High expression of genes for calcification-regulating proteins in human atherosclerotic plaques.JCI Insight, 1994
- Functional changes of aorta with massive accumulation of calciumAtherosclerosis, 1989
- 1,25-dihydroxyvitamin D3 stimulates 45Ca2+-uptake by cultured vascular smooth muscle cells derived from rat aortaBiochemical and Biophysical Research Communications, 1988