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This is one of two research projects studying anabolic treatments for osteoporosis. KU Leuven is the home institution for this project. To view the Melbourne-based partner project, click here.
With ageing our bones become brittle and prone to fractures, known as osteoporosis. Despite widespread use of therapies blocking bone loss, osteoporosis represents a major public health concern. There is a large clinical need for bone-building (osteo-anabolic) treatments that sustainably improve bone mass in patients. Intermittent parathyroid hormone (iPTH), the first-approved osteo-anabolic drug, effectively stimulates bone formation, but suspected side-effects unfortunately limit its use. Understanding the mechanisms of action of iPTH at the cellular-molecular levels could identify strategies for improved therapeutic use of this powerful drug or for developing safer new treatments. Two major angiogenic pathways (VEGF and PDGF signalling) have been identified as vital for bone formation during growth and fracture repair, along with MMP-9, a proteolytic and pro-angiogenic molecule. These pathways can jointly mediate activation and expansion of skeletal stem/progenitor cells and blood vessels, both needed for bone formation. Could this stromal-endothelial communication and vascular remodelling also be important for therapeutic bone gain? This question will be tackled here. The investigation will focus on whether VEGF, PDGF and MMP-9 are functionally involved in iPTH-induced bone formation and required for the therapeutic outcome.
This work can lead to improved or new anabolic treatment approaches for osteoporosis, based on manipulation of the stromal-vascular bone unit. The aim is to determine whether remodelling of the stromal-vascular components of the bone marrow and in cortical bone are required for the bone forming effects of iPTH treatment. Moreover, the aim is to to unravel the cellular and molecular mechanisms that mediate SSPC-endothelial cell crosstalk induced by iPTH, and how they contribute to vascular adaptations, SSPC activation, and the osteo-anabolic outcome of iPTH treatment. This will determine whether VEGF and PDGFR signalling and MMP-9 activity are required for iPTHinduced bone formation.
The specific aims are:
The University of Melbourne – Prof Natalie Sims
KU Leuven – A/Prof Christa Maes
Click on the researcher's name above to learn more about their publication and grant successes.
We are seeking a PhD candidate with the following skills:
To apply for this joint PhD opportunity, and to view the entry requirements, visit How to apply.
Apply for a joint PhD with the Toronto-Melbourne Research Training Group.
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