Bone Cell Biology & Disease

Current research projects

• Understanding how bone degenerates with age in men and women

  Age-related osteoporosis occurs, in part, because the vascular pores within the hardened outer shell of bone (the cortex) become larger with age. We are using the Melbourne Femur Research Collection, a unique forensic collection of human femur bones from healthy adults across the entire adult age range. We are using these samples to assess whether new bone produced by older men and women is structurally compromised. We will identify regions of bone loss by micro-computed tomography, index the cell populations within the pores by histology, and measure the composition of the bone that remains by synchrotron-based infra-red spectroscopy.

  Signals that control cortical porosity

  Cortical bone (the bone’s outer shell) forms through a process of consolidation, including the closure of blood vessel-impregnated channels. It is essential that some vascularised channels remain, to provide nutrients to bone cells and to allow egress of bone marrow cells, such as neutrophils, to the circulation. During ageing, these channels within the cortex expand, leading to skeletal fragility. Although the process is not understood, we have shown that it may be associated with increased JAK-STAT signalling in osteocytes, cells embedded within the bone matrix. We are now testing to see whether increased JAK-STAT signalling causes age-related cortical porosity, and whether this is mediated through a signal that promotes vascularisation.

  Control of bone mineral content by osteocytes

  The quantity of bone in the skeleton is not the only thing that makes it strong. Bone can be more fragile if the material is poor quality; an example of this is if there is too much calcified mineral in the bone, which leads to increased ‘brittleness’.

  Through our work on the Eph/Ephrin family of tyrosine kinases, we discovered that this protein is important for osteoblasts and osteocytes to control the way that bone becomes a hardened, mineralised tissue. Our continuation of this work, in collaboration with the Australian Synchrotron, is helping us to discover how collagen and bone mineral are incorporated into the skeleton in a way that makes it strong.

  Understanding bone formation on the periosteum

  Our third approach to understanding determinants of bone strength is to discover pathways that specifically stimulate the activity of cells located at the periosteum (exterior surface of cortical bone). This approach has emerged from the knowledge that increased bone formation on the outer surface of bone is more efficient at increasing bone strength than to deposit bone on the inner surface.

  We are using genetically altered mice with thickened cortical bone, along with lineage tracing (genetically introduced fluorescent labels), to identify and track periosteal cell populations. By studying the cells and molecular mechanisms involved, our goal is to identify novel targets and pathways that may be used in future to improve bone strength.