Factors That Affect Knee Structure In Healthy Women
Funder
National Health and Medical Research Council
Funding Amount
$199,176.00
Summary
Osteoarthritis (OA) has the largest impact of any chronic disease on burden of disease borne in later life, affecting women more often than men. The importance of OA has been acknowledged by its listing within musculoskeletal disease, the 7th health priority in Australia. It is 4 times as common in women as in men.Treatments which slow or prevent OA progressing are limited, so prevention must play a key role. With increasing disease severity, joint cartilage is lost. We have recently developed a ....Osteoarthritis (OA) has the largest impact of any chronic disease on burden of disease borne in later life, affecting women more often than men. The importance of OA has been acknowledged by its listing within musculoskeletal disease, the 7th health priority in Australia. It is 4 times as common in women as in men.Treatments which slow or prevent OA progressing are limited, so prevention must play a key role. With increasing disease severity, joint cartilage is lost. We have recently developed a method to measure joint cartilage from magnetic resonance imaging (MRI) scans which is able to assess the severity of structural changes in the knee. Using this method will allow us to assess 2 issues: 1) Obesity is the only identified modifiable risk factor for knee OA. However, the mechanism is poorly understood. Weight loss programs may be more effective at reducing the risk of OA if they are combined with programs aimed at maintaining muscle mass. 2) Bone is important in development of Knee OA, but its role is poorly understood. Understanding how bone metabolism relates to risk of knee OA may allow us to prevent disease. Bone is more likely to respond to pharmacological manipulation than cartilage. Thus it may prove a more effective target for intervention than cartilage. The Geelong Osteoporosis Study was begun in 1994 to study bone health in Australian women (urban and rural). Much information relevant to the risk of OA has been collected over the past decade. By performing MRI of the knee now and in 2 years time, we will determine the effect of different measures of obesity and bone metabolism on structural change at the knee which predisposes to OA. Since both of these factors (obesity and bone metabolism) are potentially modifiable, this study may offer new avenues of prevention and therapy in knee OA. This has the potential to promote a better quality of life as people age and to reduce the economic burden of knee OA in the community.Read moreRead less
The Predictors Of Knee Cartilage Loss: A 5 Year Natural History Study Based On An Existing Cohort
Funder
National Health and Medical Research Council
Funding Amount
$76,380.00
Summary
Osteoarthritis (OA) is the single biggest cause of disability in Western society. Despite this, relatively little is known about the factors that effect disease progression. This will be the first extended follow up study of cartilage volume in people with early OA. This study will build on our existing work where we have developed a cohort study of adults with early knee OA. These people were initially recruited in 1997-8. An extensive data base of potential risk factors for OA has been collect ....Osteoarthritis (OA) is the single biggest cause of disability in Western society. Despite this, relatively little is known about the factors that effect disease progression. This will be the first extended follow up study of cartilage volume in people with early OA. This study will build on our existing work where we have developed a cohort study of adults with early knee OA. These people were initially recruited in 1997-8. An extensive data base of potential risk factors for OA has been collected and both X-rays of the knee and MRI have been performed at baseline and 2 years. Extending the follow up from 2 to 5 years will allow not only more precise estimation of rates of cartilage loss and assessment of risk factors, but also enable assessment of the assumption of linearity of cartilage volume loss. It will also be possible to partition the observed variability in rates of loss into true between-subject variability and within subject residual variability. This partitioning will provide valuable information for the design of future studies in OA, similar to the establishment of statistical design principles for patterns of loss in bone mineral density.Read moreRead less
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
Bone-specific Sclerostin And SIBLING Proteins In Osteoarthritis: Novel Contributions To Cartilage And Bone Pathology
Funder
National Health and Medical Research Council
Funding Amount
$441,058.00
Summary
Arthritis is a major clinical problem and involves the destruction of cartilage in joints. However, the mechanisms of how this cartilage destruction is initiated and progresses remain poorly understood. We recently discovered that that three proteins that play a role in bone are also produced in cartilage and are increased in cartilage during osteoarthritis. We will determine the role of each of these in the disease mechanism to provide new therapeutic and biomarker targets.
I am a biochemical geneticist working on inherited disorders that affect the musculoskeletal system. My major focus is determining the molecular basis of muscular dystrophies and bone and cartilage disorders.
TRAFFICKING OF MEMBRANE SULFATE TRANSPORTERS IN THE KIDNEY
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Many diseases such as diabetes, cystic fibrosis, Alzheimer's and Parkinson's, results from a defect in the intracellular trafficking of specific membrane proteins. One important family of membrane proteins are the renal sulphate transporters, NaSi-1 and sat-1. They are two important proteins that control body sulphate homeostasis. Sulphate in the body is essential for cell matrix formation and cartilage-bone development and growth. Trafficking defects in these proteins can lead to changes in ser ....Many diseases such as diabetes, cystic fibrosis, Alzheimer's and Parkinson's, results from a defect in the intracellular trafficking of specific membrane proteins. One important family of membrane proteins are the renal sulphate transporters, NaSi-1 and sat-1. They are two important proteins that control body sulphate homeostasis. Sulphate in the body is essential for cell matrix formation and cartilage-bone development and growth. Trafficking defects in these proteins can lead to changes in serum sulphate levels, which results in softening of the bones, insufficient cartilage development, and changes in many metabolic processes. Using techniques of molecular and cellular biology, we aim to identify the precise the mechanisms that control the trafficking of these proteins in cells. This will enable us to determine how these proteins functions in both the normal and diseased states, which is currently unknown.Read moreRead less
Twist-1 Mediated Regulation Of Multipotential Mesenchymal Stem Cell Self-Renewal And Cell Fate Determination
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
In Australia, there is an increasing incidence of fractures and skeletal related problems that require surgical intervention and rehabilitation therapy. These are complex processes that involve the coordination of different bone and immune cells. We will investigate important regulatory molecules that mediate bone-cartilage stem cell recruitment and development during normal skeletal growth and remodelling. This study will help advance therapies for fracture repair and joint deterioration.
I am a molecular biologist investigating the role of SRY-SOX transcription factors in the formation and function of the gonad, and to a lesser extent, of bone, the brain and the pancreas. I also identify and functionally characterise other factors causing
The Role Of Endogenous Glucocorticoids In The Pathogenesis Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$587,697.00
Summary
Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability. Recently, we found that the development of experimental OA in mice can be slowed if the effects of the body’s own (=endogenous) glucocorticoids were blocked locally. This project will determine how endogenous glucocorticoids accelerate the development of OA. We will further test whether treatment with drugs that block the actions of endogenous glucocorticoids can slow or prevent the development of OA.
Tissue Engineering Approach To Musculoskeletal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Over the next few decades there is an anticipated steady increase in surgical intervention for bone, cartilage and tendon damages due to trauma or osteoporosis as a consequence of an aging population. These damages cause chronic pain, immobility, restricted activities, and, sometimes, death and are a considerable financial burden to the Australian Health System.