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
It is widely accepted that just under half of all people with bipolar disorder have a chronic physical illness. The one neglected comorbidity is osteoporosis. In this project, the association between bipolar disorder and bone fragility will be examined. Additionally, a potential common mechanism, systemic inflammation, which may underlie both diseases, will be investigated as a potential mediator of the relationship.
Vertebral Body Strength: Contribution Of Bone Mass, Bone Structure And Material Properties
Funder
National Health and Medical Research Council
Funding Amount
$434,498.00
Summary
This study will determine the contributions to vertebral body strength made by its structural and material properties. Using state-of-the-art computed-tomography scanners, digitised representations of vertebral bodies in three-dimensions will be produced, which enable measurement of bone structure. After strength testing of the vertebral bodies, the structural and material properties, which combine to predict vertebral body strength, will be identified in an aged population.
Caltrin As A Calcium Transport Inhibitor During Osteoclastic Bone Resorption
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Excessive bone resorption has been observed in many common bone diseases such as osteoporosis, Paget's disease and arthritis. These are major health problems in Australia and other developed countries. Increased activation or formation of osteoclasts is responsible for the excessive bone resorption. Understanding the mechanisms by which the osteoclasts exert its function and activation is an important step toward developing strategies to combat excessive bone resorption for the treatment and pre ....Excessive bone resorption has been observed in many common bone diseases such as osteoporosis, Paget's disease and arthritis. These are major health problems in Australia and other developed countries. Increased activation or formation of osteoclasts is responsible for the excessive bone resorption. Understanding the mechanisms by which the osteoclasts exert its function and activation is an important step toward developing strategies to combat excessive bone resorption for the treatment and prevention of osteolytic disorders. This project attempts to address the important and fundamental issue of osteoclast function. We have identified caltrin, a known calcium transport inhibitor, that is likely to be biologically important in osteoclast calcium homeostasis. This project intends to investigate the role of caltrin in calcium-induced apoptosis, osteoclast bone resorption and the cellular and molecular mechanisms underlined. It will enhance our knowledge of calcium regulation in osteoclasts and provide information to facilitate the development of new anti-resorptive agents.Read moreRead less
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
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
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
Clinical Efficacy Of Haematopoietic Stem Cell Transplantation In Mucopolysaccharidosis IIIA
Funder
National Health and Medical Research Council
Funding Amount
$508,051.00
Summary
Lysosomal storage disorders (LSD) are inherited diseases that affect about 1 in 7700 Australian children; all share common physical symptoms include heart and breathing difficulties, stiff joints, skeletal deformities, enlarged head, and a characteristic facial appearance. Two-thirds of patients will also develop brain disease. The lysosome is a component of each cell in the human body; its role it is to break down and remove waste from the cell. This involves a series of proteins (enzymes) that ....Lysosomal storage disorders (LSD) are inherited diseases that affect about 1 in 7700 Australian children; all share common physical symptoms include heart and breathing difficulties, stiff joints, skeletal deformities, enlarged head, and a characteristic facial appearance. Two-thirds of patients will also develop brain disease. The lysosome is a component of each cell in the human body; its role it is to break down and remove waste from the cell. This involves a series of proteins (enzymes) that act in sequence. A LSD arises when the lysosome lacks the activity of one protein in this chain. This loss of protein activity means that the waste removal process is impaired. Waste begins to 'store', clogging the cell and interfering with its usual functions. This gives rise to devastating symptoms that worsen over time as storage increases. Brain disease in LSD has profound effects on the child: mental capacity declines, they become hyperactive and aggressive and progressively lose learned skills (e.g. walking, talking) and control of bodily functions. Mucopolysaccharidosis (or MPS) type IIIA is a LSD that affects the brain. Bone marrow transplantation (BMT) is an accepted treatment for many diseases, including cancer. However, unlike cancer and some LSD, BMT does not work in MPS IIIA children. The reasons for this are unknown. This project is important in understanding the basic mechanisms that prevent this form of therapy from working in these children. If we can understand what prevents its effectiveness, we can devise methods to overcome it and potentially offer MPS IIIA (and other LSD that do not respond to BMT) a viable treatment option. We have a colony of mice affected by MPS IIIA; their symptoms are similar to that seen in humans, making them ideal for this study.Read moreRead less