The authors state that they have no conflicts of interest.
Article first published online: 17 MAR 2008
Copyright © 2008 ASBMR
Journal of Bone and Mineral Research
Volume 23, Issue 8, pages 1182–1193, August 2008
How to Cite
Davey, R. A., Turner, A. G., McManus, J. F., Chiu, W. M., Tjahyono, F., Moore, A. J., Atkins, G. J., Anderson, P. H., Ma, C., Glatt, V., MacLean, H. E., Vincent, C., Bouxsein, M., Morris, H. A., Findlay, D. M. and Zajac, J. D. (2008), Calcitonin Receptor Plays a Physiological Role to Protect Against Hypercalcemia in Mice. J Bone Miner Res, 23: 1182–1193. doi: 10.1359/jbmr.080310
Published online on March 17, 2008;
- Issue published online: 4 DEC 2009
- Article first published online: 17 MAR 2008
- Manuscript Accepted: 12 MAR 2008
- Manuscript Revised: 16 FEB 2008
- Manuscript Received: 9 JAN 2008
- bone histomorphometry
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.