title: The role of the calcitonin receptor in protecting against induced hypercalcemia is mediated via its actions in osteoclasts to inhibit bone resorption.
abstract: Despite the therapeutic value of calcitonin in treating bone disease, a biological role of endogenous calcitonin is controversial. Having previously demonstrated that the CTR has a biological role in protecting against calcium stress using a global CTRKO mouse model, the purpose of this study was to determine whether the protection conferred by the CTR during induced hypercalcemia is mediated via CTR expression on osteoclasts. Mice were generated, in which the CTR was deleted specifically within osteoclasts (OCL-CTRKOs) and compared with mice in which the CTR was deleted globally (global CTRKOs). Significantly, peak serum calcium levels following induced hypercalcemia were >18% higher in global-CTRKOs and OCL-CTRKOs than controls (P<0.01) due to increased bone resorption (P<0.05). Peak serum calcium levels relative to controls were greater in global-CTRKO males than OCL-CTRKO males (P<0.001), which may, at least in part, be due to increased reabsorption of calcium in the kidney (P<0.01). Controls for all analyses were sex-matched littermates with normal CTR expression. In conclusion, the CTR protects against hypercalcemia predominantly via its inhibitory action on osteoclasts.
authors.affiliation: Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Turner
authors.forename: Francisca
authors.initials: F
authors.lastname: Tjahyono
authors.forename: W S Maria
authors.initials: WS
authors.lastname: Chiu
authors.forename: Jarrod
authors.initials: J
authors.lastname: Skinner
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sawyer
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Moore
authors.forename: Howard A
authors.initials: HA
authors.lastname: Morris
authors.forename: David M
authors.initials: DM
authors.lastname: Findlay
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Davey
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005260:Female; D005838:Genotype; D006934:Hypercalcemia / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018003:Receptors, Calcitonin; D002117:Calcitriol; D002118:Calcium