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

Davey, Rachel A., Turner, Andrew G., McManus, Julie F., Chiu, W.S. Maria, Tjahyono, Francisca, Moore, Alison J., Atkins, Gerald J., Anderson, Paul H., Ma, Cathy, Glatt, Vaida, MacLean, Helen E., Vincent, Cristina, Bouxsein, Mary, Morris, Howard A., Findlay, David M., & Zajac, Jeffrey D. (2008) Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice. Journal of Bone and Mineral Research, 23(8), pp. 1182-1193.

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Abstract

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 Cre/loxP 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)2D3]-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.

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ID Code: 70890
Item Type: Journal Article
Refereed: Yes
Keywords: calcitonin, knock-out/in, bone histomorphometry
DOI: 10.1359/JBMR.080310
ISSN: 08840431
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2008 American Society for Bone and Mineral Research
Deposited On: 02 May 2014 03:20
Last Modified: 06 Jun 2014 05:59

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