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

Rachel A. Davey; Andrew G. Turner; Julie F. McManus; W. S.Maria Chiu; Francisca Tjahyono; Alison J. Moore; Gerald J. Atkins; Paul H. Anderson; Cathy Ma; Vaida Glatt; Helen E. MacLean; Cristina Vincent; Mary Bouxsein; Howard A. Morris; David M. Findlay; Jeffrey D. Zajac

doi:10.1359/jbmr.080310

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

Rachel A. Davey, Andrew G. Turner, Julie F. McManus, W. S.Maria Chiu, Francisca Tjahyono, Alison J. Moore, Gerald J. Atkins, Paul H. Anderson, Cathy Ma, Vaida Glatt, Helen E. MacLean, Cristina Vincent, Mary Bouxsein, Howard A. Morris, David M. Findlay, Jeffrey D. Zajac

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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.

Original language	English (US)
Pages (from-to)	1182-1193
Number of pages	12
Journal	Journal of Bone and Mineral Research
Volume	23
Issue number	8
DOIs	https://doi.org/10.1359/jbmr.080310
State	Published - Aug 2008
Externally published	Yes

Keywords

Bone histomorphometry
Calcitonin
Knock-out/in

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Orthopedics and Sports Medicine

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10.1359/jbmr.080310

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Davey, R. A., Turner, A. G., McManus, J. F., Chiu, W. S. 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., & Zajac, J. D. (2008). Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice. Journal of Bone and Mineral Research, 23(8), 1182-1193. https://doi.org/10.1359/jbmr.080310

Davey, RA, Turner, AG, McManus, JF, Chiu, WSM, Tjahyono, F, Moore, AJ, Atkins, GJ, Anderson, PH, Ma, C, Glatt, V, MacLean, HE, Vincent, C, Bouxsein, M, Morris, HA, Findlay, DM & Zajac, JD 2008, 'Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice', Journal of Bone and Mineral Research, vol. 23, no. 8, pp. 1182-1193. https://doi.org/10.1359/jbmr.080310

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title = "Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice",

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.",

keywords = "Bone histomorphometry, Calcitonin, Knock-out/in",

author = "Davey, {Rachel A.} and Turner, {Andrew G.} and McManus, {Julie F.} and Chiu, {W. S.Maria} and Francisca Tjahyono and Moore, {Alison J.} and Atkins, {Gerald J.} and Anderson, {Paul H.} and Cathy Ma and Vaida Glatt and MacLean, {Helen E.} and Cristina Vincent and Mary Bouxsein and Morris, {Howard A.} and Findlay, {David M.} and Zajac, {Jeffrey D.}",

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doi = "10.1359/jbmr.080310",

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AU - Chiu, W. S.Maria

AU - Tjahyono, Francisca

AU - Moore, Alison J.

AU - Atkins, Gerald J.

AU - Anderson, Paul H.

AU - Ma, Cathy

AU - Glatt, Vaida

AU - MacLean, Helen E.

AU - Vincent, Cristina

AU - Bouxsein, Mary

AU - Morris, Howard A.

AU - Findlay, David M.

AU - Zajac, Jeffrey D.

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

Abstract

Keywords

ASJC Scopus subject areas

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