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
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
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
Are Chondrocytes The Target Cells Of Glucocorticoid Therapy In Autoimmune Arthritis?
Funder
National Health and Medical Research Council
Funding Amount
$544,619.00
Summary
Glucocorticoids (GCs) are widely used for their potent anti-inflammatory and immunomodulatory effects due to the effects GCs on immune cells or synovial fibroblasts. Recently, we have made the exciting discovery that arthritis mice with glucocorticoid receptor knock-out in chondrocyte are completely resistant to glucocorticoid treatment. This study will identify the mechanisms underlying these hormonal effects with the aim to find new targets for efficient treatments for arthritis.
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.
MicroRNAs As Therapeutic Targets For Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$921,754.00
Summary
microRNAs are small cellular RNA fragments that regulate protein expression. They have been shown to be crucial regulators of normal development and are associated with many disease processes. The goal of this project is to determine the role of microRNAs in the initiation and progression of joint degeneration in osteoarthritis and test the therapeutic efficacy of targeting microRNAs as new approach to OA treatment.
ARC, A Newly Identified Regulator Of Chondrocyte Differentiation And Death, Is A Novel Therapeutic Target For OA
Funder
National Health and Medical Research Council
Funding Amount
$763,983.00
Summary
We have identified a critical regulator of the survival and normal metabolism of the cells in articular cartilage. Loss of this molecule is an early event in joint injury that leads to osteoarthritis (OA). The current proposal will determine the mechanisms whereby this protein functions to protect cartilage breakdown in OA, how its levels in chondrocytes are regulated in both healthy and diseased conditions, and at what stages of disease increasing its expression protects against OA progression.
The Calcium Channel TRPV4 In Skeletal Development And Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$683,069.00
Summary
We have discovered that mutations in a calcium channel gene, TRPV4, cause an inherited osteoarthritis in the hands and feet. This work suggests that TRPV4 may be important in osteoarthritis and suggests the exciting possibility that modulating TRPV4 activity may provide a new therapeutic approach for arthritis. We will study how and why the mutations disrupt channel function and study mouse models to see if they are more or less susceptible to arthritis.
Hype Or Hope? Platelet-Rich Plasma As A Symptom- And DisEaSe-modifying Treatment FOR Knee OstEoarthritis - The RESTORE Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,400,359.00
Summary
Knee osteoarthritis (OA) is a major public health problem worldwide with no cure. Thus safe and effective treatments that reduce symptoms and slow structural disease progression are needed. This clinical trial aims to test the effects of injections of platelet-rich plasma (a blood product) into the knee on pain and joint structure in 288 people with knee OA. The results will provide high quality evidence to determine whether platelet rich plasma should be used to treat knee OA.