A Controlled Longitudinal Study Of Knee Cartilage Volume If The Offspring Of Subjects With Osteoarthritis Of The Knee.
Funder
National Health and Medical Research Council
Funding Amount
$144,392.00
Summary
Osteoarthritis is the most common cause of musculoskeletal disability and cost in Australia. Both genetic and environmental factors have been implicated as causes of this disease. As yet, however, there are no proven strategies for prevention of this very common condition and treatment of established disease is unsatisfactory. Part of the reason for this is the fact that there is no sensitive and accurate measure of early disease. In this study, we plan to evaluate knee cartilage volume assessed ....Osteoarthritis is the most common cause of musculoskeletal disability and cost in Australia. Both genetic and environmental factors have been implicated as causes of this disease. As yet, however, there are no proven strategies for prevention of this very common condition and treatment of established disease is unsatisfactory. Part of the reason for this is the fact that there is no sensitive and accurate measure of early disease. In this study, we plan to evaluate knee cartilage volume assessed by magnetic resonance imaging. This is a promising new candidate which is both accurate and sensitive. We will be measuring knee volume both cross-sectionally and longitudinally in the offspring of patients who have had knee replacement for osteoarthritis and comparing them to randomly selected controls to see if knee volume can be utilised as a marker of early or asymptomatic disease particularly in identifying which treatments may be effective at preventing osteoarthritis in later life.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
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.
Glycomic Control Of Cartilage Extra Cellular Matrix Turnover
Funder
National Health and Medical Research Council
Funding Amount
$706,289.00
Summary
Small, naturally occurring glycomic molecules control cartilage matrix turnover. We have synthesised small synthetic analogues of the naturally occurring molecules, and demonstrated their ability to regulate signalling pathways. This project will test and mathematical model the synthetic molecules in cell and tissue assays to define their properties and tissue effects, and assess their suitability as a drug delivery system. The results will be an important step towards designing new ways of trea ....Small, naturally occurring glycomic molecules control cartilage matrix turnover. We have synthesised small synthetic analogues of the naturally occurring molecules, and demonstrated their ability to regulate signalling pathways. This project will test and mathematical model the synthetic molecules in cell and tissue assays to define their properties and tissue effects, and assess their suitability as a drug delivery system. The results will be an important step towards designing new ways of treating osteoarthritis and other cartilage diseases.Read moreRead less
Molecular Mechanisms Of Cartilage Degeneration In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$457,517.00
Summary
Arthritis affects 15% of the entire Australian population and 50% in people over 60. The most common form of joint disease by far is osteoarthritis (OA). One of the central features of OA is the breakdown of the cartilage that covers the ends of bones in joints, and this is a major determinant of the long term outcome and need for joint replacement surgery. There are no current therapies that halt or reverse cartilage breakdown in OA. This is largely due to our incomplete understanding of the mo ....Arthritis affects 15% of the entire Australian population and 50% in people over 60. The most common form of joint disease by far is osteoarthritis (OA). One of the central features of OA is the breakdown of the cartilage that covers the ends of bones in joints, and this is a major determinant of the long term outcome and need for joint replacement surgery. There are no current therapies that halt or reverse cartilage breakdown in OA. This is largely due to our incomplete understanding of the molecular changes and pathways involved in both the onset and progression of cartilage breakdown. Powerful new genomic approaches allow simultaneous screening of changes in a broad profile of genes, particulalrly in humans and mice following complete sequencing of their genomes. By applying this new technology in the earliest stages of cartilage degeneration in OA, the role of novel genes and the pathways involved in the onset of this disease process can be discovered. However, to investigate changes at the initiation of disease, tissue from animal rather than human joints must be used due to the difficulty in obtaining pre-symptomatic human cartilage. In order to maximise the number of genes screened, cartilage from a novel surgically induced model of OA in mice will be used in this study. We have developed micro dissection and linear mRNA amplification methods to overcome inherent problems with tissue availability from this small animal species. Successful completion of these studies will for the first time allow identification of the complex changes that occur in early OA. An important and likely outcome of this research will be identification of novel matrix proteins and regulatory molecules that will provide critical information for the development of new diagnostic and therapeutic approaches to OA.Read moreRead less