Calcitonin Receptor Plays a Physiological Role to Protect Against Hypercalcemia in Mice

Overview

Journal J Bone Miner Res

Publisher Oxford University Press

Date 2008 Jul 17

PMID 18627265

Citations 28

Authors

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

Affiliations

Soon will be listed here.

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)(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.

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