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


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.
Orita
Yuichi
Y
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Yamamoto
Hideya
H
Kohno
Nobuoki
N
Sugihara
Masaaki
M
Honda
Hiroaki
H
Kawamata
Seiichi
S
Mito
Shinji
S
Soe
Nwe Nwe
NN
Yoshizumi
Masao
M
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000473:pathology*; D002114:Calcinosis / Q000473:pathology*; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000473:pathology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053244:Osteoprotegerin / Q000235:genetics / Q000502:physiology*; D014815:Vitamins / Q000008:administration & dosage*
D053244:Osteoprotegerin; D014815:Vitamins; D000469:Alkaline Phosphatase; D002117:Calcitriol; D002118:Calcium