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
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 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
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.
Biomechanics of the human spine measured using magnetic resonance imaging. Statistics show that 80% of the population suffer back pain at some time. However, because the spine is very complex our understanding of its mechanics and the causes of back pain are still limited. This project will investigate the anatomy and activity of the spinal muscles and the behaviour of the intervertebral disc in living subjects using innovative Magnetic Resonance Imaging techniques. Significant outcomes will be ....Biomechanics of the human spine measured using magnetic resonance imaging. Statistics show that 80% of the population suffer back pain at some time. However, because the spine is very complex our understanding of its mechanics and the causes of back pain are still limited. This project will investigate the anatomy and activity of the spinal muscles and the behaviour of the intervertebral disc in living subjects using innovative Magnetic Resonance Imaging techniques. Significant outcomes will be new definitive descriptions of the detailed anatomy of the spine and its mechanisms. This will enhance the accuracy and detail of models under development for predicting spinal function following disease, injury or surgical procedures.Read moreRead less