Role of osteoprotegerin in arterial calcification development of new animal model

被引:70
作者
Orita, Yuichi
Yamamoto, Hideya
Kohno, Nobuoki
Sugihara, Masaaki
Honda, Hiroaki
Kawamata, Seiichi
Mito, Shinji
Soe, Nwe Nwe
Yoshizumi, Masao
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Cardiovasc Physiol & Med, Minami Ku, Hiroshima 7348551, Japan
[2] Hiroshima Univ, Grad Sch Biomed Sci, Dept Mol & Internal Med, Minami Ku, Hiroshima 7348551, Japan
[3] Hiroshima Univ, Grad Sch Hlth Sci, Dept Dev Biol, Minami Ku, Hiroshima 7348551, Japan
[4] Hiroshima Univ, Grad Sch Hlth Sci, Res Inst Radiat Biol & Med, Dept Anat & Histol,Minami Ku, Hiroshima 7348551, Japan
关键词
osteoprotegerin; alkaline phosphate; vascular smooth muscle cells; calcium deposits;
D O I
10.1161/ATVBAHA.107.147868
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 alpha, 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.
引用
收藏
页码:2058 / 2064
页数:7
相关论文
共 40 条
  • [1] Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: A national study
    Block, GA
    Hulbert-Shearon, TE
    Levin, NW
    Port, FK
    [J]. AMERICAN JOURNAL OF KIDNEY DISEASES, 1998, 31 (04) : 607 - 617
  • [2] Blumenthal Herman T., 1944, AMER JOUR PATH, V20, P665
  • [3] BONE MORPHOGENETIC PROTEIN EXPRESSION IN HUMAN ATHEROSCLEROTIC LESIONS
    BOSTROM, K
    WATSON, KE
    HORN, S
    WORTHAM, C
    HERMAN, IM
    DEMER, LL
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (04) : 1800 - 1809
  • [4] osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
    Bucay, N
    Sarosi, I
    Dunstan, CR
    Morony, S
    Tarpley, J
    Capparelli, C
    Scully, S
    Tan, HL
    Xu, WL
    Lacey, DL
    Boyle, WJ
    Simonet, WS
    [J]. GENES & DEVELOPMENT, 1998, 12 (09) : 1260 - 1268
  • [5] Vascular pericytes express osteogenic potential in vitro and in vivo
    Doherty, MJ
    Ashton, BA
    Walsh, S
    Beresford, JN
    Grant, ME
    Canfield, AE
    [J]. JOURNAL OF BONE AND MINERAL RESEARCH, 1998, 13 (05) : 828 - 838
  • [6] Regulation of vascular calcification - Roles of phosphate and osteopontin
    Giachelli, CM
    Speer, MY
    Li, XW
    Rajachar, RM
    Yang, H
    [J]. CIRCULATION RESEARCH, 2005, 96 (07) : 717 - 722
  • [7] OSTEOPONTIN IS ELEVATED DURING NEOINTIMA FORMATION IN RAT ARTERIES AND IS A NOVEL COMPONENT OF HUMAN ATHEROSCLEROTIC PLAQUES
    GIACHELLI, CM
    BAE, N
    ALMEIDA, M
    DENHARDT, DT
    ALPERS, CE
    SCHWARTZ, SM
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (04) : 1686 - 1696
  • [8] Progression of aortic calcification is associated with metacarpal bone loss during menopause - A population-based longitudinal study
    Hak, AE
    Pols, HAP
    van Hemert, AM
    Hofman, A
    Witteman, JCM
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (08) : 1926 - 1931
  • [9] Osteoprotegerin: a link between osteoporosis and arterial calcification?
    Hofbauer, LC
    Schoppet, M
    [J]. LANCET, 2001, 358 (9278) : 257 - 259
  • [10] Hui MZ, 1998, ANAT REC, V253, P91