Signalling Through A Bioactive Aggrecan Fragment: What Is The Mechanism?
Funder
National Health and Medical Research Council
Funding Amount
$431,347.00
Summary
Osteoarthritis (OA) affects approximately 20% of Australians. There are no therapies that modify the course of the disease and joint replacement surgery is expensive and invasive. We have discovered that a peptide product of cartilage breakdown (the 32mer) signals cartilage cells to mount an inflammatory and catabolic response. We will determine how the 32mer triggers this response, whether other joint cells are similarly activated and how it can be stopped, with the goal of pursuing new targets ....Osteoarthritis (OA) affects approximately 20% of Australians. There are no therapies that modify the course of the disease and joint replacement surgery is expensive and invasive. We have discovered that a peptide product of cartilage breakdown (the 32mer) signals cartilage cells to mount an inflammatory and catabolic response. We will determine how the 32mer triggers this response, whether other joint cells are similarly activated and how it can be stopped, with the goal of pursuing new targets for therapyRead moreRead less
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
Extracellular Signal-Regulated Kinases 1 And 2 Activity In Osteoarthiritis
Funder
National Health and Medical Research Council
Funding Amount
$387,071.00
Summary
Osteoarthritis (OA) is the most common form of joint disorders and a major cause of disability in the elderly, affecting approximately 60% of men and 75% of woman above the age of 65. This project will specifically focus on the regulatory role of cell signaling pathways in OA development and progression. The outcome of this project is the potential to develop early intervention treatments of osteoarthritis.
Gene Mining For Novel Molecular Determinants Of The Skeleton
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
Musculoskeletal conditions affect over 6 million Australians and research has shown that genetic background strongly influences development of these disorders. This project will identify genes that have a role in controlling bone and joint architecture. Identification of these genes will assist in the development of treatments targeting bone disorders and allow screening for these genes to provide an opportunity for people to take preventative action to improve bone and joint health.
Effect Zoledronic Acid And Risedronate On The Preservation Of The Femoral Head In A Rat Model Of Perthes Disease
Funder
National Health and Medical Research Council
Funding Amount
$199,750.00
Summary
Perthes Disease (Legg-Perthes Disease) is a common childhood disorder, which leads to collapse and deformity of the growing hip joint. This can lead to arthritis in adult life, as well as a short leg on the affected side. The cause is as yet unknown. A class of drugs called bisphosphonates has been shown to help children with osteogenesis imperfecta (brittle bone disease). We believe, based on our extensive studies of the effect of these drugs on bone healing, that they could also help children ....Perthes Disease (Legg-Perthes Disease) is a common childhood disorder, which leads to collapse and deformity of the growing hip joint. This can lead to arthritis in adult life, as well as a short leg on the affected side. The cause is as yet unknown. A class of drugs called bisphosphonates has been shown to help children with osteogenesis imperfecta (brittle bone disease). We believe, based on our extensive studies of the effect of these drugs on bone healing, that they could also help children with Perthes disease. Although proving to be safe and effective in children with osteogenesis imperfecta, before exposing children with Perthes disease to the risk of any side effects, animal studies are needed. A certain type of rat called the spontaneously hypertensive rat gets a condition almost exactly the same as Perthes disease. This study will treat a large number of these rats and perform detailed study into whether it has a positive effect on preserving the shape of the hip joint, as well as looking into how this actually occurs. A successful outcome would pave the way for trials in children with Perthes disease, and could result in the avoidance of surgery and improved health outcomes for the children.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