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 Therapeutic Value Of Targeting Wnt Signalling For The Treatment Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$561,535.00
Summary
Osteoarthritis (OA) affects 1.62 million Australians and imposes a significant burden on healthcare. It is characterised by damage to joint cartilage, and increased bone formation with formation of bone spurs. Our studies will determine the importance of the Wnt signalling pathway in mediating OA joint degeneration and identify mechanisms that regulate the activation of this pathway in OA. This will inform the development of novel therapeutic strategies which could halt joint damage in OA.
Monocyte Chemotactic Protein-1 (MCP1) And The PTH Anabolic Effect In Bone.
Funder
National Health and Medical Research Council
Funding Amount
$690,435.00
Summary
Chemokines and their receptors are major regulators of cell-cell interactions in many tissues. This project explores the strong increase of monocyte chemotactic protein-1 (MCP1 or CCL2) in bone, in a treatment where parathyroid hormone (a controller of calcium homeostasis) is used to increase bone mass to prevent osteoporosis. MCP1 was previously thought to be an inflammatory regulator, induced during infection and important in autoimmune conditions, so its role in bone was highly unexpected.
New Approaches To The Prevention And Treatment Of Musculoskeletal Disease
Funder
National Health and Medical Research Council
Funding Amount
$466,492.00
Summary
In Australia, musculoskeletal conditions like osteoarthritis and back pain are responsible for much pain and disability. Although until recently these were considered to be purely due to wear and tear, Associate Professor Wluka, a rheumatologist, has shown that these are not simply due to overuse and loading but metabolic factors also play a role. This award will enable the role of these factors to be examined and new therapies tested in clinical trials, providing evidence to improve the managem ....In Australia, musculoskeletal conditions like osteoarthritis and back pain are responsible for much pain and disability. Although until recently these were considered to be purely due to wear and tear, Associate Professor Wluka, a rheumatologist, has shown that these are not simply due to overuse and loading but metabolic factors also play a role. This award will enable the role of these factors to be examined and new therapies tested in clinical trials, providing evidence to improve the management of these conditions.Read moreRead less
Sclerostin Is A Key Regulator Of Wnt Signalling In Bone And Cartilage Pathology In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$590,945.00
Summary
Osteoarthritis (OA) is the most widespread bone and joint problem in Australia with has enormous social and economic consequences. We have identified Sclerostin (SOST) as a key regulator of the signalling pathway that drives the increase in production of bone and the erosion of cartilage in joints that are the hallmark of OA. The aims of the present project are to determine the effect altering SOST activity on the initiation and progression of OA.
Functional Variants Of RUNX2 Related To Bone Density
Funder
National Health and Medical Research Council
Funding Amount
$451,938.00
Summary
Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant in a gene called RUNX2 that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. This variant is highly correlated with changes in the second promoter of RUNX2, such that the high bone density form appears to be the ....Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant in a gene called RUNX2 that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. This variant is highly correlated with changes in the second promoter of RUNX2, such that the high bone density form appears to be the ancestral form of this gene. We now need to know how this change in this promoter alters bone density and we are following up on observations that other important transcription factors bind to the variable site in the promoter. Furthermore, we have assembled a large collection of samples from people who have had extensive measures of bone density and arthritis in order to accurately measure the impact of this gene on bone density, osteoarthritis and bone fracture. In addition, some people with bone fracture at the hip, or low bone density, have mutations in this gene. Such mutations in a region called the Q-repeat are rather common, 1-200 people are carriers. Our data show that these mutant proteins are not as efficient at their task of regulating other genes. We now want to know how this occurs in a molecular sense, since it is known that the Runx2 protein resides in the nucleus of the cell and interacts with many other regulators. This part of the project is being done with one of the world experts on gene regulation in bone cells. Since RUNX2 is a master regulator of the cells that make bone, this gives hope that it may be possible to alter bone formation through this master regulator.Read moreRead less
Improving The Prevention And Outcomes Of Knee And Hip Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
Osteoarthritis is a major public health problem. No current treatment slows disease progression with end-stage osteoarthritis treated by joint replacement surgery. This project will identify new approaches for the prevention and treatment of osteoarthritis and the improvement of patients’ outcomes after total joint replacement surgery. The findings will have both public health and clinical impact, informing clinical practice of strategies to improve the prevention and outcomes of osteoarthritis.
Chondrocyte Hypertrophy In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$360,018.00
Summary
Whereas chondrocyte hypertrophy is a normal feature of skeletal growth, in adult chondrocytes it is associated with osteoarthritis (OA). We propose that collagen II fragments provide signals for hypertrophy in cartilage. The lack of collagen II fragments in our collagenase-resistant mouse provides a unique opportunity to address the role of collagen II fragments in driving cellular hypertrophy. We will identify bioactive collagen II fragments that represent novel targets for OA therapies