Dr Allison Pettit
Research Interests
Osteal macrophages (osteomacs): their role in bone dynamics and
therapeutic potential to treat bone diseases.
Musculoskeletal diseases (e.g. osteoporosis) are commonly
chronic incurable diseases that have devastating morbidity and also
increased mortality. Together with orthopaedic fractures, they cost
the Australian health system over $10 billion annually, a burden
that will continue to increase with the ageing population. Current
empiric therapies are good at preventing bone loss but these drugs
do not restore bone that has already been lost and only reduce
fracture risk by approximately 50% when used to treat osteoporosis.
There is a clear need for better affordable therapies that not only
halt bone loss but also promote the appropriate regeneration of new
bone. We are undertaking research is the emerging field of
osteoimmunology, which explores the complex interactions between
the immune and bone systems.
Resident tissue macrophages are important for host immune
defence and also participate in normal tissue processes and repair.
My research has described a novel osteal macrophage population,
osteomacs, which are located within the specialized tissues that
line all bones. Osteomacs form a striking 'canopy structure' that
encapsulates sites of bone formation and bone remodelling,
indicating that these cells are principle participants in these
essential processes. Using a tibial injury model in conjunction
with Mafia transgenic mice, in which conditional in vivo
osteomac depletion can be achieved, we have demonstrated that
osteomacs promote bone formation and healing. Bone repair (measured
as type I collagen matrix deposition) was inhibited by 53% in
osteomac deplete compared to replete mice. My research team has
several projects in progress with the aim of dissecting the
mechanism by which osteomacs regulate bone dynamics. Overall, this
cutting edge research is providing significant contributions to the
basic understanding of bone physiology and is striving to improve
the current standard of therapy for many bone diseases and skeletal
trauma.
Research Projects
Delineate the functional role of osteomacs in bone
remodelling
Bone remodelling (involves sequential resorption and formation
events) is the essential process involved in maintenance of
skeletal integrity in adults and failure of appropriate remodelling
causes the prevalent disease osteoporosis. While we have localized
osteomacs to sites of bone remodelling we have not yet delineated
their functional contribution to this complex process. This
research project will use both in vitro and in
vivo strategies to delineate the role of osteomacs in bone
remodelling and will determine if inappropriate osteomac function
occurs in osteoporosis.
Identification of osteomac anabolic bone factors
Using a microarray approach we have identified several candidate
osteomac anabolic factors. This research project will validate
these factors using both in vitro primary cell based
assays and in vivo transgenic/knockout models and
recombinant protein treatment. Validation of these anabolic factors
is a critical first step in the development of new generation bone
anabolic drugs.
Demonstrate that targeting osteomacs and/or their function is a
useful clinical tool to improve fracture repair.
My research group is using clinically relevant in vivo
fracture models in conjunction with the mafia transgenic mice and
recombinant molecule therapies to confirm the essential
contribution of macrophages to bone healing. This research will
determine the potential clinical benefit of manipulating osteomacs
in order to replace bone lost due to disease and/or complex
fracture.
PhD Projects available
- Macrophage regulation of the hematopoietic stem cell niche
- A novel osteoimmunological approach to identify anabolic bone
therapies for osteoporosis & fracture repair
Chang MK*, Raggatt LJ*, Alexander KA, Kuliwaba JS, Fazzalari NL,
Schroder K, Maylin ER, Ripoll VM, Hume DA and Pettit
AR. Osteal tissue macrophages are intercalated throughout
human and mouse bone lining tissues and regulate osteoblast
function in vitro and in vivo. Journal of Immunology,
2008, 15;181(2):1232-44. (IF: 6.1/ Citations 3; May 05; *authors
contributed equally to this work).(IF: 6.9/Citations 180; May
09).
Pettit AR, Quinn C, MacDonald KPA, Cavanagh LL,
and Thomas G, Townsend W, Handel M, Thomas R.Nuclear localization
of RelB is associated with effective antigen-presenting cell
function. Journal of Immunology, 1997:
159(8), 3681-91. (IF: 6.7/Citations 105; May 09)
Reviews
Pettit AR, Hume DA and Raggatt LJ. Osteal
Macrophages: A new twist on coupling during bone dynamics.
Bone 2008, 15;181(2):1232-44. (IF: 6.2 /Citations 1; May
05)
Contact details and email
Allison Pettit PhD.
The University of Queensland
Centre for Clinical Research
Building 71/918, Royal Brisbane Hospital
Herston QLD Australia 4092
email: a.pettit@uq.edu.au
phone: 3346 5528
