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
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.
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
Improving Patient Outcome Following Arthroscopic Autologous Chondrocyte Implantation
Funder
National Health and Medical Research Council
Funding Amount
$345,591.00
Summary
Autologous chondrocyte implantation (ACI) is the ‘gold standard’ for treating knee cartilage defects. Traditionally, ACI was performed through open surgery. However, ACI can now be performed through ‘keyhole’ surgery, decreasing the co-morbidity of open surgery. Furthermore, optimal patient outcome is limited by a lack of knowledge in effective post-operative rehabilitation. This project will evaluate outcomes following ACI performed through keyhole surgery, in conjunction with 'accelerated' reh ....Autologous chondrocyte implantation (ACI) is the ‘gold standard’ for treating knee cartilage defects. Traditionally, ACI was performed through open surgery. However, ACI can now be performed through ‘keyhole’ surgery, decreasing the co-morbidity of open surgery. Furthermore, optimal patient outcome is limited by a lack of knowledge in effective post-operative rehabilitation. This project will evaluate outcomes following ACI performed through keyhole surgery, in conjunction with 'accelerated' rehabilitation.Read moreRead less
A Novel Strategy For The Treatment Of Chronic Skeletal Joint Defects
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Skeletal joint injuries often heal poorly with current treatment approaches and lead to the onset of osteoarthritis. This project will produce a synthetic graft with unique properties to mimic the complex structure of joint tissues, and high bioactivity to induce optimal healing of the joint. This graft will constitute a viable alternative for the treatment of skeletal joint defects, resulting in significant healthcare benefits and improved long-term outcomes.
The Role Of Endogenous Glucocorticoids In The Pathogenesis Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$587,697.00
Summary
Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability. Recently, we found that the development of experimental OA in mice can be slowed if the effects of the body’s own (=endogenous) glucocorticoids were blocked locally. This project will determine how endogenous glucocorticoids accelerate the development of OA. We will further test whether treatment with drugs that block the actions of endogenous glucocorticoids can slow or prevent the development of OA.
Osteoarthritis (OA) affects approximately 20% of Australians and costs billions each year in joint replacements. Therapies that halt joint destruction in OA are urgently needed. We hypothesise that the little-known gene, vanin -3, is a key regulator of OA disease pathways. Our project will map vanin-3 in the joint and reveal how much vanin-3 contributes to joint destruction in mice. We expect to find a link between vanin-3 and metabolic disorders and identify new targets for therapy.
There is an urgent need for engineered tissue repair and replacement components for cartilage implantation in damaged joints due to a shortage of donor tissue. This project will generate smart composite biomaterials with enhanced mechanical strength and physical properties that are desirable for cartilage repair. The fabricated scaffolds will mimic the microstructure of native cartilage and are next-generation biomaterials designed to facilitate cartilage regeneration.
In Australia osteoarthritis is the leading cause of pain and disability with the majority of individuals displaying radiographic evidence of this condition by age 65. We are developing two novel technologies which use patients' own stem cells to repair damaged cartilage. This project involves both the advancement of these technologies as well as their evaluation using a sheep cartilage repair model. These technologies offer significant promise for those suffering joint pain.