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

5 minute read

Cross-section of corticol bone

This is one of two research projects studying anabolic treatments for osteoporosis. Melbourne is the home institution for this project. To view the KU Leuven-based partner project, click here.

Cortical bone 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. In contrast, during ageing, cortical pores, and the blood vessel network within the cortex expands. Neither of these processes are understood, but both are likely to be caused by communication between stromal cells, which differentiate into bone-forming osteoblasts, and the vasculature. The project seeks to identify how the vasculature and osteoblasts communicate to facilitate the development of cortical bone, the toughened outer shell of all skeletal elements. Cortical bone forms by consolidation of a porous, highly vascularised embryonic bone structure. This includes selected closure of blood vessel-impregnated pores, leaving some available for egress of bone marrow cells to the periphery. Cortical pore closure is controlled by communication between bone-forming osteoblasts, their precursors, and the vasculature through two molecules (VEGF and SOCS3, previously studied independently by the Maes and Sims laboratories).

Project goals

This work can lead to improved or new anabolic treatment approaches for osteoporosis, based on manipulation of the stromal-vascular bone unit.  The overall aim is to identify the first signalling pathway by which osteoblasts control cortical bone trans-vascularisation:

  1. Define the cortical and medullary vascular phenotypes and pattern of VEGF expression in the SOCS3 deficient mouse model.
  1. Determine whether elevated osteocytic VEGF generates a defect in cortical structure and vascularity.
  1. Determine whether osteocyte-targeted loss of VEGF rescues the SOCS3 deficient phenotype.

Supervision team

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.

Who we are looking for

We are seeking a PhD candidate with the following skills:

  • Demonstrated experience in the field of medicine/physiology
  • Demonstrated experience with scientific computation
  • Demonstrated ability to work independently and as part of a team
  • Demonstrated time and project management skillsDemonstrated ability to write research reports or other publications to a publishable standard (even if not published to date)
  • Excellent written and oral communication skills
  • Demonstrated organisational skills, time management and ability to work to priorities
  • Demonstrated problem-solving abilities.

Further details

  • The PhD candidate will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.
  • The collaboration between A/Prof Christa Maes and Prof Natalie Sims is designed to build a strong network of researchers interested in the cross-tissue communication that exists within the skeleton, and between the skeleton and other organ systems in the body. Future research work will make use of the resources developed in these projects (such as RNAseq data on samples collected, additional tissue samples from the murine studies, communication pathways identified) to fully characterise the interactions between the vasculature and bone formation in both marrow and trabecular contexts in models of skeletal disease and disrepair, including age-related bone loss, fracture healing, multiple myeloma, breast cancer metastases, and chronic kidney disease. All of these have well-established murine models that will be interrogated with our combined technical expertise, shared and duplicated across the two institutions., The Sims lab has developed a mouse model of delayed cortical consolidation, caused by cell-targeted genetic deletion of SOCS3 (Suppressor of Cytokine Signalling 3). These mice also have porous cortical bone with abnormally high cortical vascularisation, and high mRNA levels of vascular markers including VEGF. The Maes lab has extensive experience studying bone marrow vasculature and the effects of VEGF signalling in osteoblasts and their precursors in the skeleton.
  • This PhD project will be based at the University of Melbourne with a minimum 12-month stay at KU Leuven.
  • The candidate will be enrolled in the PhD program at the St Vincent's Hospital/University of Melbourne and in the PhD program at the Department of Development and Regeneration at KU Leuven.

To apply for this joint PhD opportunity, and to view the entry requirements, visit How to apply.

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