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

J Bone Miner Res. 2008 Aug;23(8):1182-93. doi: 10.1359/jbmr.080310.


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)(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Actins / metabolism
  • Animals
  • Calcitonin / blood
  • Calcitriol / pharmacology
  • Calcium / blood
  • Female
  • Femur / anatomy & histology
  • Femur / pathology
  • Gene Deletion
  • Gene Targeting
  • Hypercalcemia / metabolism
  • Hypercalcemia / prevention & control*
  • Integrases / metabolism
  • Isoenzymes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Phenotype
  • Receptors, Calcitonin / metabolism*
  • Tartrate-Resistant Acid Phosphatase


  • Actins
  • Isoenzymes
  • Receptors, Calcitonin
  • Calcitonin
  • Cre recombinase
  • Integrases
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Calcitriol
  • Calcium