on July 5, 2007
Published online before print July 5, 2007, doi: 10.1161/ATVBAHA.107.147868
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 30, 2006
Accepted on June 22, 2007
Role of Osteoprotegerin in Arterial Calcification. Development of New Animal Model
Yuichi Orita ;
From the Department of Molecular and Internal Medicine (Y.O., H.Y., N.K., M.S.), Graduate School of Biomedical Sciences, the Department of Developmental Biology (H.H.), Research Institute for Radiation Biology and Medicine, the Department of Anatomy and Histology (S.K.), Graduate School of Health Sciences, and the Department of Cardiovascular Physiology and Medicine (S.M., N.N.S., M.Y.), Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
* To whom correspondence should be addressed. E-mail: yos1956oktbh{at}hiroshima-u.ac.jp.
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 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.
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.
This article has been cited by other articles:
 |
|
 |
|
  S. Kwan Tat, N. Amiable, J.-P. Pelletier, C. Boileau, D. Lajeunesse, N. Duval, and J. Martel-Pelletier Modulation of OPG, RANK and RANKL by human chondrocytes and their implication during osteoarthritis Rheumatology, September 17, 2009; (2009) kep300v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mizobuchi, D. Towler, and E. Slatopolsky Vascular Calcification: The Killer of Patients with Chronic Kidney Disease J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1453 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nybo and L. M Rasmussen The capability of plasma osteoprotegerin as a predictor of cardiovascular disease: a systematic literature review Eur. J. Endocrinol., November 1, 2008; 159(5): 603 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Hsu, Y. Tintut, and L. L. Demer Vitamin D and Osteogenic Differentiation in the Artery Wall Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1542 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Demer and Y. Tintut Vascular Calcification: Pathobiology of a Multifaceted Disease Circulation, June 3, 2008; 117(22): 2938 - 2948. [Full Text] [PDF]
|
|