Dr Allison Pettit

Bones and Immunology

Musculoskeletal diseases and injury are a leading cause of chronic disability and are a substantial and increasing burden on health systems and individuals worldwide. Prevention and treatment of many bone diseases is currently inadequate. Macrophages have been indirectly implicated in many bone diseases, linking aberrant macrophage function to bone damage. However it was our recent discovery of specialized macrophages within bone tissues (osteomacs) that highlighted macrophages have a prominent and direct role in bone physiology and disease. Osteomacs are associated with sites of bone formation, bone resorption and bone remodelling and can directly control the function of the specialized cells that build and remove bone. Our ongoing research is investigating the molecular mediators involved in this communication and the impact of positively or negatively targeting macrophages on reaching and maintaining peak bone health.

We are also investigating the contribution of macrophages to bone repair after injury/fracture. Fracture repair can be broken down into 3 basic phases: inflammatory (clean up the injury and gather repair components), anabolic (form a temporary boney structure bridging the injury) and catabolic (remodel the temporary structure to re-instate normal bone architecture and mechanics). Our results show that macrophages are essential for establishing bone repair during the early inflammatory phase of bone healing. A sustained presence of macrophages is also required for optimal bone repair during the anabolic phase. Our research is examining whether macrophages can be targeted to accelerate fracture repair. Also under investigation is whether aberrant macrophage biology is an underlying cause of the compromised bone healing commonly associated with co-morbidities such as osteoporosis, diabetes, obesity and chronic inflammatory disease.

Our third research focus is the contribution of resident bone marrow (BM) macrophages, including osteomacs, to hematopoietic stem cell (HSC) biology. This is in collaboration with the Stem Cell Biology and Cancer and Stem Cell Groups within the Mater Research Blood and Bone Program. The region in BM that is closest to bone surfaces (endosteum) has been shown to be the preferred site of residence of true HSC and contains specialized environments called endosteal stem cell niches. We have shown that osteomacs/macrophages are an integral component of these niches. Our specific interest is to determine if osteomacs/macrophages are required for successful bone marrow/HSC transplantation and whether enhancing osteomacs/macrophages is a viable strategy for improving transplantation outcomes.

Major Projects:

1. Targeting macrophages as a therapeutic strategy for accelerating or correcting healthy and compromised fracture healing.
2. The role of macrophages in facilitating haematopoietic stem cell engraftment and reconstitution.
3. Elucidation of the molecular mediators responsible for osteomac regulation of osteoblast and osteoclast function.
4. Phenotypic and functional characterization of resident macrophages populations in periosteum, endosteum and central bone marrow.