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
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.
A Prospective Study To Identify The Mechanical Causes And Methods For Early Detection Of Knee Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Knee osteoarthritis is a great cost to society, financially and in quality of life. Anti-inflammatory drugs are commonly used to treat the symptoms, but many people receive joint replacements to stop pain and improve function. We need to prevent osteoarthritis, but the causes for this common disease are largely unknown. Animal studies have shown two particular mechanical factors that cause osteoarthritis, which are seen in the walking and running, or gait, patterns of some people. We call these ....Knee osteoarthritis is a great cost to society, financially and in quality of life. Anti-inflammatory drugs are commonly used to treat the symptoms, but many people receive joint replacements to stop pain and improve function. We need to prevent osteoarthritis, but the causes for this common disease are largely unknown. Animal studies have shown two particular mechanical factors that cause osteoarthritis, which are seen in the walking and running, or gait, patterns of some people. We call these pathological gait patterns as they impose larger-than-normal forces on the knee's articular surfaces. We measure these knee forces with our new computer knee model coupled with data that we measure in a gait analysis laboratory. These forces may cause knee osteoarthritis in humans, but this is still unknown. Currently there is no simple medical test to detect the early onset of knee osteoarthritis. The bones in the knee are one of the first structures to show osteoarthritic changes. Using our new computerised analysis of high definition X-ray of the knee we can identify subtle differences in the knee due to osteoarthritis. This will be compared with changes to joint assessed using MRI. Osteoarthritis develops slowly in normal people, so to study progression of knee osteoarthritis we need a human population that has a higher risk of developing the disease. Partial meniscectomy in the knee is a common surgery performed to improve knee function in those who have suffered a knee meniscus injury. However, partial meniscectomy patients have a high risk of developing knee osteoarthritis. Therefore, using partial meniscectomy patients we are investigating if pathological gait patterns cause knee osteoarthritis, measuring the development of the disease with our new X-ray methods. With the gait analysis methods we can also identify the movements that characterise these pathological gait patterns so we can formulate rehabilitation programmes to help prevent knee osteoarthritis.Read moreRead less
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.