The physiological role of the calcitonin receptor in bone and calcium homeostasis

  • Project Lead

    Associate Professor Rachel Davey
    T: +61 3 9496 5507
    E: r.davey@unimelb.edu.au
    W: Personal web page

    Location: Level 7, Lance Townsend Building, Studley Road, Austin Health, Heidelberg

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

Collaborators

  • Prof David Findlay, Dept of Orthopaedics and Trauma, University of Adelaide, SA
  • A/Prof Paul Anderson, University of South Australia, SA, Australia
  • Prof Gerald Atkins, Dept of Orthopaedics and Trauma, University of Adelaide, SA, Australia

Funding

  • NHMRC Project Grant, "The actions of the hormone, calcitonin, on bone and calcium metabolism."
  • Ian Potter Foundation, "Translation of bone biology research into better treatments for osteoporosis, cancer and arthritis."
  • Rebecca Cooper Grant, "The action of the hormone, calcitonin, to regulate bone formation."

Research Outcomes

  • 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.
  • Davey RA*, Dacquin R*, Laplace C, Levasseur R, Morris HA, Goldring SR, Gebre-Medhin S, Galson DL, Zajac JD, Karsenty G. (*Equal first authors) Amylin inhibits bone resorption while the CT receptor controls bone formation in vivo. Journal of Cell Biology 2004; 164(4):509-514.
  • WSM Chiu, JF McManus, AJ Notini, AI Cassady, JD Zajac, RA Davey. Transgenic mice that express Cre recombinase in osteoclasts. Genesis 2004; 39(3):178-85.

Research Group

Molecular Endocrinology and Musculoskeletal Research Group




Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Medicine and Radiology

Unit / Centre

Molecular Endocrinology and Musculoskeletal Research Group