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

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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 languageEnglish (US)
Pages (from-to)1182-1193
Number of pages12
JournalJournal of Bone and Mineral Research
Volume23
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

Keywords

  • Bone histomorphometry
  • Calcitonin
  • Knock-out/in

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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