The Role Of Suppressor Of Cytokine Signalling-3 (SOCS-3) In Chondrocytes During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$348,392.00
Summary
Cytokines are messenger proteins produced and secreted from one cell which then bind to specific receptors on the surface of other cells. After binding, a series of intracellular events occurs, termed signalling, that results in the target cell changing its behaviour. Cytokine signalling, if allowed to proceed unchecked, can result in various disease states. The suppressor of cytokine signalling (SOCS) proteins are key negative regulators of cytokine signalling within the cell. They are induced ....Cytokines are messenger proteins produced and secreted from one cell which then bind to specific receptors on the surface of other cells. After binding, a series of intracellular events occurs, termed signalling, that results in the target cell changing its behaviour. Cytokine signalling, if allowed to proceed unchecked, can result in various disease states. The suppressor of cytokine signalling (SOCS) proteins are key negative regulators of cytokine signalling within the cell. They are induced by a wide range of stimuli, especially from a group called the IL-6 family. We have preliminary data showing that cartilage cells (chondrocytes) normally produce a particular SOCS protein, called SOCS-3. We have also shown that when SOCS-3 production is dysregulated, the chondrocytes undergo excessive proliferation. Normal chondrocyte function is important during skeletal development and diseases such as osteoarthritis are thought to result from abnormal chondrocyte behaviour. It is likely that SOCS-3 has a key role in regulating chondrocyte function. The aim of this proposal is therefore to examine the role of SOCS-3 in chondrocytes, during development and in disease. Much of our understanding of the role of the SOCS proteins comes from the construction of mutant mice that lack a particular SOCS protein. When mutant mice are made that lack SOCS-3 in the whole animal the mice die before birth and so virtually nothing is known about the role of SOCS-3 in chondrocytes and the implications for cartilage in disease states, such as arthritis. To answer this we will create mice that lack SOCS-3 specifically in their chondrocytes. Evaluating the role of SOCS-3 in cartilage development and chondrocyte function during degenerative and inflammatory disease states is potentially of major clinical importance in improving our understanding of arthritis and of cartilage repair.Read moreRead less
Proteomics Of Arthritis: Exploring Mechanisms Of Cartilage Degradation And Biomarker Identification
Funder
National Health and Medical Research Council
Funding Amount
$592,034.00
Summary
Arthritis is a major clinical and socio-economic problem. Arthritis involves the destruction of cartilage in joints. However, the mechanisms of initiation and progression of cartilage destruction remain poorly understood. Our studies will use new proteomic approaches to identify the changes in protein synthesis and degradation in mouse models of arthritis. This will provide critical information on disease mechanisms and for the development of diagnostic biomarkers and therapeutic approaches
Economic Evaluation And Health Outcomes Of Arthritis And Its Treatments
Funder
National Health and Medical Research Council
Funding Amount
$360,660.00
Summary
Musculoskeletal diseases are the most common single cause of chronic disability in Australia and total joint replacement is rapidly becoming one of the most commonly performed operations. This burden of illness is likely to increase with our ageing population and there is an urgent need to obtain data relating to the costs and outcomes in the Australian context so that appropriate planning of health services and resources can be carried out. The WHO (World Health Organisation) has declared 2000 ....Musculoskeletal diseases are the most common single cause of chronic disability in Australia and total joint replacement is rapidly becoming one of the most commonly performed operations. This burden of illness is likely to increase with our ageing population and there is an urgent need to obtain data relating to the costs and outcomes in the Australian context so that appropriate planning of health services and resources can be carried out. The WHO (World Health Organisation) has declared 2000 to 2010 the Bone and Joint Decade, recommending that research into musculoskeletal disorders be a priority. We have been recruiting and following a unique cohort of osteoarthritis and rheumatoid arthritis patients, from both the public and private health sectors, who have been carefully documenting their health outcomes, health care costs (including primary, revision and bilateral hip and knee joint replacement surgery), out-of-pocket and indirect costs related to their arthritis. Long-term follow-up is now essential to obtain a clear picture of the impact of living with arthritis over time and the cost-effectiveness and predictors of good and bad outcomes of joint replacement surgery. The information derived from this study will be useful for patients and doctors in making their decisions about treatments, as well as for health care providers in planning of health services for arthritis sufferers. Given that the cohorts are already established, the study is in a unique position to provide ongoing important longer-term data for relatively low cost.Read moreRead less
Novel Pathways Involving APC And PAR-2 In Cartilage Degradation In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$448,834.00
Summary
Loss of the cartilage that normally lines the ends of bones is central to joint failure in arthritis and the need for replacement surgery. There are presently no treatments that stop cartilage breakdown in joint disease. This project investigates the role of a new pathway not previously thought to be active in cartilage, in the progressive damage seen in arthritis. Successful completion of these studies may provide a novel new strategy to treat joint disease.
The Australian Study Of Cost And Utilities Related To Osteoporotic Fractures
Funder
National Health and Medical Research Council
Funding Amount
$411,627.00
Summary
The research will quantify the cost and quality of life impact of fragility fractures in Australia. The study design is based on an international study - International Costs and Utilities Related to Osteoporotic Fracutres Study (ICUORS) that aims to investigate the impact of osteoporosis-related fractures of the hip, spine and wrist. Results can be used to compare cost-effectiveness of different drugs and lifestyle interventions aiming to decrease the burden of osteoporosis in Australia.
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.
Examining Psychological State In Patients Presenting For Arthritis Surgery
Funder
National Health and Medical Research Council
Funding Amount
$347,792.00
Summary
Total joint replacement (TJR) is a common surgical procedure in Australia (80,000 per year). Pre-operative psychological distress has been reported to be between 30-60% in TJR patients and is associated with pain and poor recovery. Little is known about the nature of psychological distress in those presenting for TJR. This study aims to identify the psychological profile of TJR patients who experience suboptimal recovery and in doing so inform future programs that aim to enhance psychological we ....Total joint replacement (TJR) is a common surgical procedure in Australia (80,000 per year). Pre-operative psychological distress has been reported to be between 30-60% in TJR patients and is associated with pain and poor recovery. Little is known about the nature of psychological distress in those presenting for TJR. This study aims to identify the psychological profile of TJR patients who experience suboptimal recovery and in doing so inform future programs that aim to enhance psychological well-being in patients on waiting lists for TJRRead moreRead less
The early osteoarthritis (OA) phenotype. Australia like many other developed countries is undergoing a major demographic shift involving significant growth in the aged population. From both a patient perspective and a societal perspective, research into the underlying determinants of osteoarthritis such as those outlined in this proposal are of great importance to the aged population. Nearly one in five Australians has arthritis; indeed more Australians have arthritis than any other national hea ....The early osteoarthritis (OA) phenotype. Australia like many other developed countries is undergoing a major demographic shift involving significant growth in the aged population. From both a patient perspective and a societal perspective, research into the underlying determinants of osteoarthritis such as those outlined in this proposal are of great importance to the aged population. Nearly one in five Australians has arthritis; indeed more Australians have arthritis than any other national health priority condition. From an individual point-of-view, the pain and disability due to osteoarthritis (OA) can lead to loss of independence and diminished in quality of life for older adults.Read moreRead less