Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice

被引：66

作者：

Davey, Rachel A. ^{[1
]}

Turner, Andrew G. ^{[1
]}

McManus, Julie F. ^{[1
]}

Chiu, W. S. Maria ^{[1
]}

Tjahyono, Francisca ^{[1
]}

Moore, Alison J. ^{[2
]}

Atkins, Gerald J. ^{[2
,3
]}

Anderson, Paul H. ^{[2
]}

Ma, Cathy ^{[1
]}

Glatt, Vaida ^{[4
,5
]}

MacLean, Helen E. ^{[1
]}

Vincent, Cristina ^{[2
]}

Bouxsein, Mary ^{[4
,5
]}

Morris, Howard A. ^{[2
]}

Findlay, David M. ^{[2
,3
]}

Zajac, Frey D. ^{[1
]}

机构：

[1] Univ Melbourne, Dept Med, Heidelberg, Vic 3084, Australia

[2] IMVS, Hanson Inst, Adelaide, SA, Australia

[3] Univ Adelaide, Dept Orthopaed & Trauma, Adelaide, SA, Australia

[4] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[5] Harvard Univ, Sch Med, Boston, MA USA

来源：

JOURNAL OF BONE AND MINERAL RESEARCH | 2008年 / 23卷 / 08期

关键词：

calcitonin; knock-out/in; bone histomorphornetry;

D O I：

10.1359/JBMR.080310

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

It is well established that calcitonin is a potent inhibitor of bone resorption; however, a physiological role for calcitonin acting through its cognate receptor, the calcitonin receptor (CTR), has not been identified. Data from previous genetically modified animal models have recognized a possible role for calcitonin and the CTR in controlling bone formation; however, interpretation of these data are complicated, in part because of their mixed genetic background. Therefore, to elucidate the physiological role of the CTR in calcium and bone metabolism, we generated a viable global CTR knockout (KO) mouse model using the CrelloxP system, in which the CTR is globally deleted by > 94% but < 100%. Global CTRKOs displayed normal serum ultrafiltrable calcium levels and a mild increase in bone formation in males, showing that the CTR plays a modest physiological role in the regulation of bone and calcium homeostasis in the basal state in mice. Furthermore, the peak in serum total calcium after calcitriol [1,25 (OH)(2)D-3] -induced hypercalcemia was substantially greater in global CTRKOs compared with controls. These data provide strong evidence for a biological role of the CTR in regulating calcium homeostasis in states of calcium stress.

引用

页码：1182 / 1193

页数：12

共 40 条

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