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STAT3 signaling and the role of stromal-vascular communication in the development of cortical bone

PhD project

This is one of two research projects studying ways to improve anabolic treatments for osteoporosis, and is co-supervised between The University of Melbourne and KU Leuven. To view the KU Leuven-based partner project, click here.

Cortical bone (bone’s outer shell) forms through a process of consolidation, including the closure of blood vessel-impregnated pores. However, it is essential that some vascularised pores remain, to enable egress of bone marrow cells, such as neutrophils, to the circulation. During ageing, these pores within the cortex expand. Although this process is not understood, it is likely to involve communication between stromal cells, which differentiate into bone-forming osteoblasts, and the vasculature. This project seeks to identify how the vasculature and osteoblasts communicate to facilitate the development and degradation of cortical bone, the toughened outer shell of all skeletal elements.

To determine the specific molecules and cells that contribute to cortical porosity, the student and team will use genetically modified mouse models, including inducible and site-specific mouse mutants, fluorescent cryohistology and light sheet microscopy, and will apply bone phenotyping methods as micro-CT, histomorphometry and high-resolution 3D confocal vascular imaging.

One of the features we have noted in this model is a high level of vascularisation within the cortex, which could contribute to the high cortical porosity. In the currently vacant PhD position, the student will use this model and a range of image analysis techniques to understand the bone and vascular signalling pathways that drive high cortical porosity.

The overall aim is to identify the first signalling pathway by which osteoblasts control cortical bone trans-vascularisation, which could ultimately lead to improved or new anabolic treatment approaches for osteoporosis. This project will include a portion of work conducted at KU Leuven in Belgium.

Supervised by:

·  Prof Natalie Sims

·  Prof Christa Maes (KU Leuven)

·  Dr Natalie Wee

Supervised by:

  • Prof Natalie Sims
  • Disease Focus:

  • Osteoporosis
  • Research Unit:

  • Bone cell biology & disease
  • The laboratory of Professor Sims (The University of Melbourne and St Vincent’s Institute of Medical Research) studies cortical bone development and the processes by which cortical bone degenerates over time. In our previous work, we have developed methods for measuring cortical bone maturation during bone growth, and have established a mouse model with high cortical porosity due to increased JAK-STAT signalling within bone.

    For further information about this project, contact: [email protected]