Characterising the physiological role of the calcitonin receptor in bone and calcium homeostasis
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Associate Professor
Rachel Davey+61 3 9496 5507
Project Details
Calcitonin acting via its receptor, the calcitonin receptor (CTR), has well documented potent inhibitory effects on osteoclasts, the cells responsible for bone breakdown. In young animals and in times of high bone metabolism, calcitonin can acutely lower blood calcium levels. There is also evidence for calcitonin actions in the kidney, to decrease tubular reabsorption of calcium, and a number of actions have been reported in the brain and hypothalamus. These effects have been observed with exogenous calcitonin and the physiological roles of calcitonin have not been amenable to study. The aim of this project is to characterise calcitonin’s important and related physiological roles in (a) protecting the skeleton by regulating bone metabolism and (b) maintaining calcium homeostasis. This will be achieved by using a number of in vivo mouse models in which the calcitonin receptor has been genetically modified. These studies will significantly advance our understanding of the physiological role of calcitonin, which is important in appreciating the totality of calcium homeostasis in the body and, equally important, in unravelling the control of bone metabolism.
Researchers
- Associate Professor Rachel Davey, Group Leader
- Professor Jeffrey Zajac, Academic Lead
Collaborators
- Professor David Findlay, Dept of Orthopaedics and Trauma, University of Adelaide, SA
Funding
- NHMRC Project Grant
- Ian Potter Foundation
- The Rebecca L Cooper Medical Research Foundation
Research Publications
- Clarke MV, Russell PK, Findlay DM, Sastra S, Anderson PH, Skinner JP, Atkins GJ, Zajac JD, Davey RA. A role for the calcitonin receptor to limit bone loss during lactation in female mice by inhibiting osteocytic osteolysis. Endocrinology, 2015, 156(9):3203-3214.
- Davey RA and Findlay DM. Calcitonin – Physiology or Fantasy? Journal of Bone and Mineral Research Invited Review. 2013, 28(5):973-979.
- Turner AG, Tjahyono F, Chiu WSM, Skinner J, Sawyer R, Moore AJ, Morris HA, Findlay DM, Zajac JD, Davey RA. “The role of the calcitonin receptor in protecting against induced hypercalcemia is mediated via its actions in osteoclasts to inhibit bone resorption”. Bone 2011, 48, 354-361.
- Davey R.A., Turner A., McManus J.F., Chiu W., 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.. The calcitonin receptor plays a physiological role to protect against hypercalcemia in mice. Journal of Bone and Mineral Research 2008 23(8):1182-93.
- Davey RA, Moore AJ, Chiu WSM, Notini AJ, Morris HA, Zajac JD. The effects of amylin deficiency on trabecular bone in young mice are sex dependent. Calcified Tissue International 2006; 78(6), 398-403.