The Role Of Endogenous Glucocorticoids In Autoimmune Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$693,185.00
Summary
Inflammatory joint diseases affect millions of people worldwide and in most patients these often chronic conditions can not be cured. In an experimental model of arthritis we have found that bone cells can modify the severity of inflammation when certain hormonal signals are blocked. This study will identify the mechanisms underlying these hormonal effects with the aim to find new targets for efficient treatments for arthritis.
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.
Novel Roles For IL-33 In The Maintenance Of Bone Mass And As A Locally Derived Anabolic Factor For Bone
Funder
National Health and Medical Research Council
Funding Amount
$592,574.00
Summary
Over 10% of the population have thin, brittle bones that fracture easily, and is often seen in elderly people. When diagnosed, a fracture has usually already occurred and the bone is already thin. Drugs are available to stop further bone weakening, but building new bone would be best. We have found a protein in bone that reduces bone loss and stimulates bone formation processes. This project seeks to determine how this protein works and how to exploit it to design new bone building therapies.
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.
The Arthroplasty And Bariatric Surgery (ABS) Study: A Randomised Controlled Trial Of Laparoscopic Adjustable Gastric Banding Prior To Total Knee Arthroplasty
Funder
National Health and Medical Research Council
Funding Amount
$664,149.00
Summary
Knee replacement is a common surgical procedure in Australia (40,000 per year). More than 60% of this group are obese and this is associated with higher early (clinical) and long term (implant) survival complications. Laparoscopic adjustable gastric banding (LAGB) is an effective and safe means of achieving sustained weight loss. This study compares the outcomes of total knee replacement in groups of obese patients who have and have not undergone pre-knee replacement LAGB.
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.
Pathobiology Of The Small Leucine Rich Repeat Proteoglycans In Cartilage, Intervertebral Disc And Tendon Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$516,625.00
Summary
Back problems (M$700), OA (M$600), muscle and tendon disorders (M$500) accounted for 60% of musculoskeletal (MSK) health care expenditure in Australia in 1993-1994, were the second most common cause of presentations to a general practitioner, the third leading contributor to health system expenditure (>$3 billion) and accounted for ~300,000 hospital admissions, ~15 million medical services and over 13 million prescriptions. Significant disability due to MSK disease were noted in ~50% of peopl ....Back problems (M$700), OA (M$600), muscle and tendon disorders (M$500) accounted for 60% of musculoskeletal (MSK) health care expenditure in Australia in 1993-1994, were the second most common cause of presentations to a general practitioner, the third leading contributor to health system expenditure (>$3 billion) and accounted for ~300,000 hospital admissions, ~15 million medical services and over 13 million prescriptions. Significant disability due to MSK disease were noted in ~50% of people aged 65 years. Australian census data indicates that ageing trends will result in an increased incidence of MSK conditions as the longevity of the Australian population rises, exerting an ever increasing burden on the healthcare budget. Extreme levels of sporting or physical activity from traumatic loading of joints can lead to excessive loading of collagen fibres in MSK tissues leading to their failure and loss of tissue function. Common end stages of collagen fibre breakdown are preceded by matrix changes which may predispose MSK tissues to enzymatic and mechanical damage. One such change is an increased degradation of a family of small leucine-rich proteoglycans (SLRPs) which modulate the diameter, strength and assembly of collagen fibrils and bind and modify the effects of reparative growth factors and degradative cytokines within connective tissues. Altered synthesis of SLRPs and SLRP fragments have been identified in abnormal intervertebral disc, cartilage and tendon. Very little is known however about how these fragments are generated within these tissues and how they affect growth factor binding or collagen fibril formation. This deficiency will be addressed in our proposed study which will provide novel information on mechanisms of cartilage, intervertebral disc and tendon degeneration and potential therapeutic and diagnostic targets which may be exploited in future studies on the treatment of these musculoskeletal conditions.Read moreRead less
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
In Vivo Patellofemoral Joint Measurement Using Kinematic Radiostereometric Analysis (RSA)
Funder
National Health and Medical Research Council
Funding Amount
$141,000.00
Summary
Complications following total knee joint replacement continue to be a major cause for revision surgery and leads to a significant financial burden in terms of health care expenditure. Recent studies suggest that many of these complications are associated with post-surgical pain from the patella knee cap joint, commonly termed anterior knee pain (AKP). Post-surgery AKP may be influenced by the motion of the patella. Recent prospective, randomised trials have compared clinical outcomes between peo ....Complications following total knee joint replacement continue to be a major cause for revision surgery and leads to a significant financial burden in terms of health care expenditure. Recent studies suggest that many of these complications are associated with post-surgical pain from the patella knee cap joint, commonly termed anterior knee pain (AKP). Post-surgery AKP may be influenced by the motion of the patella. Recent prospective, randomised trials have compared clinical outcomes between people with TKA in which the patellar surface is replaced (patellar resurfacing) or retained, but have been unable to accurately account for differences in patellar movement in those people with post-surgery complications. To date, studies of patellar motion after total knee replacement have been limited to two-dimensional analyses. This study addresses the technological limitations of previous trials by utilising accurate techniques for directly measuring skeletal motion using kinematic radiostereometric analysis (RSA). These data will measure patellar kinematics in three-dimensions for the first time. This information will allow optimisation of the design of TKA and the surgical techniques required for their implantation. Furthermore, the results will assist in the identification of surgical indications for patellar resurfacing, and the kinematic factors associated with anterior knee pain following total knee replacement surgery.Read moreRead less