The Role Of Perlecan In Tensional Connective Tissues
Funder
National Health and Medical Research Council
Funding Amount
$605,037.00
Summary
Musculoskeletal diseases affect tension and weight bearing connective tissues which have notoriously poor repair capabilities. These conditions are difficult to treat clinically and surgical repair in many cases does not provide a return to optimal joint function impinging on the quality of life of afflicted individuals and their carers. Our project aims to better understand the structure and function of these tissues in health and disease with a view to improving repair strategies.
Osteal Macrophages As Therapeutic Targets For Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$618,015.00
Summary
Fragility fracture associated with osteoporosis is a substantial health problem costing $1.62 billion to treat in 2012 in Australia. There is no approved therapy to improve and accelerate fracture healing to help reduce this increasing health burden. This research will advance understanding of fracture repair in healthy and osteoporotic bone and progress development of a fracture therapy to improve bone repair by promoting specialised immune cells.
Cell Biology Of Stress Fractures: Activation Of Remodelling At Sites Of Non-union
Funder
National Health and Medical Research Council
Funding Amount
$493,817.00
Summary
Stress fractures are debilitating injuries. We characterised a model of stress fractures in rat ulnae, learning that they heal by activated remodelling, that key genes are expressed in a temporal pattern, and that part of the fracture remains un-healed, similar to many clinical cases. Now, we will examine cell localisation of important genes necessary for remodelling, and test the efficacy of different growth factors to activate a healing response in the non-healed section of the fracture.
Molecular And Histopathological Investigation Of Stress Fracture Healing And Effects Of Anti-inflammatory Drugs.
Funder
National Health and Medical Research Council
Funding Amount
$412,652.00
Summary
Stress fractures are debilitating injuries affecting children, adolescents and adults in sport, and army recruits. They also occur in horse and greyhound racing, often resulting in euthanasia of the animals involved. They incur considerable costs in medical expenses, time lost from sport and interruption to military training. But, there is almost no information on the mechanism of healing of these fractures. Non-steroidal anti-inflammatory drugs (NSAIDs) are still the most widely used medication ....Stress fractures are debilitating injuries affecting children, adolescents and adults in sport, and army recruits. They also occur in horse and greyhound racing, often resulting in euthanasia of the animals involved. They incur considerable costs in medical expenses, time lost from sport and interruption to military training. But, there is almost no information on the mechanism of healing of these fractures. Non-steroidal anti-inflammatory drugs (NSAIDs) are still the most widely used medication in management of musculoskeletal injuries, yet their effect on healing of stress fractures is unknown. NSAIDs delay fracture healing, but until recently there has been no standardised way of studying stress fractures. We have created, for the first time, a well-characterised, non-invasive model of stress fractures in the forearm of rats that closely resembles the clinical situation. This provides a novel and unique opportunity to determine the histological and molecular mechanism of stress fracture healing, and to investigate effects of antiinflammatory-analgesic medications on this process. Rats will have an experimental stress fracture produced in one forelimb, and its healing will be examined up to ten weeks using microscopic investigation and analysis of the genes that are turned off or on to initiate the process. Groups of rats will also be treated with antiinflammatory drugs such as ibuprofen, specific COX-2 inhibitors and a new class of drugs that target early immune responses called C5a receptor antagonists. The analgesic Paracetamol will also be investigated as an alternative to the NSAIDs described above. There is widespread use of anti-inflammatory agents in managing stress fractures, so it is vital that their effects on stress fracture healing be examined. This project has enormous significance for optimising approaches for clinical management of stress fractures and for understanding the interaction of anti-inflammatory or analgesic agents in that process.Read moreRead less
Delayed bone healing can be a considerable problem in both children and adults. Up to 10% of fractures fail to heal properly. An advanced understanding of the cellular responses in bone repair and their manipulation could improve the lives of many patients with orthopaedic problems. These studies will advance out knowledge of interventions to promote bone healing which could be translated rapidly into clinical care.
Mesenchymal Progenitor Cells And Intervertebral Disc Repair
Funder
National Health and Medical Research Council
Funding Amount
$754,223.00
Summary
Low back pain affects 80% of the general population and is a major social and economic burden thus there is a clear need for effective treatment. Annual direct and indirect costs for low back pain exceeded $100 billion in the USA in 2006. We will use bone marrow derived multipotent progenitor cells in a regenerative strategy to undertake repair of the intervertebral disc in an ovine mechanical destabilisation model which reproduces early degenerative changes similar to those evident in man.