Tendon injury is one of the most common health problems worldwide and affects almost everyone at some point in particular the aging populaiton. However, the current treatments are not well defined. We identifed an extracellular molecules SPARC that potentially plays an important role in tendon function. The aim of this study is to examine the role of SPARC in tendon development, homestasis and degenerative using transgenic mice and gene therapy. We predict that SPARC will have therapeutic value ....Tendon injury is one of the most common health problems worldwide and affects almost everyone at some point in particular the aging populaiton. However, the current treatments are not well defined. We identifed an extracellular molecules SPARC that potentially plays an important role in tendon function. The aim of this study is to examine the role of SPARC in tendon development, homestasis and degenerative using transgenic mice and gene therapy. We predict that SPARC will have therapeutic value for the treatment of tendinopathy.Read moreRead less
Rotator cuff (RC) tendon disease is a huge burden on the healthcare system in Australia and a major cause of morbidity in our aging population. Disorders of the RC are the most common cause of shoulder pain, which accounts for 1.2% of all visits to general practitioners. The prevalence of RC pathology increases with age to reach 30-50% by the seventh decade of life and a staggering 70-80% by the ninth. While most cases are treated conservatively, there are over 12,000 RC repair surgeries perform ....Rotator cuff (RC) tendon disease is a huge burden on the healthcare system in Australia and a major cause of morbidity in our aging population. Disorders of the RC are the most common cause of shoulder pain, which accounts for 1.2% of all visits to general practitioners. The prevalence of RC pathology increases with age to reach 30-50% by the seventh decade of life and a staggering 70-80% by the ninth. While most cases are treated conservatively, there are over 12,000 RC repair surgeries performed annually in Australia, with patients being committed to a prolonged convalescence. There are no drug therapies to specifically treat RC or other tendon injuries and many surgical repairs fail within 12 months. The limited treatment options for RC and other tendon disorders stems from a lack of knowledge of the molecular changes that precede and lead to rupture. It is recognised that the content of sulphated sugars or glycosaminoglycans (GAGs) on proteoglycans in tendon is the strongest predictor of the tisues strength. Accumulation of GAG is a well-recognised feature of torn tendons in man. The changes in proteoglycan synthesis and breakdown that precede and lead to tendon rupture have not been defined. We have developed a new model of shoulder tendon injury in sheep that induces regional degeneration mimicking that seen in human RC disorders. We have found changes in expression of specific proteoglycans and their degradative enzymes in early tendon disease. The current project will use this model in combination with a novel culture system and recently developed genetically modified mice to determine for the first time the changes that occur over time in proteoglycan metabolism that are responsible for tendon degeneration that leads to rupture. Successful completion of these studies will identify biomarkers to monitor disease progression and a platform for the development of new therapeutic strategies to treat this debilitating disorder.Read moreRead less
Degeneration and tearing of tendons such as the rotator cuff is a major health issue in working and ageing Australians. Tendon ruptures are preceded by degenerartive change which contributes to the poor success with surgical repair. There are very limited medical treatments available. We have developed an animal model mimicing human tendon dgeneration and will determine the utility and mechanisms of action of using a novel new therapy, stem cells in modulating degenerarion and aiding repair.
SPARC Induced Tendon Differentiation And Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$154,718.00
Summary
Tendinopathy has a significant patient morbidity, which is a clear burden to the Australian economy. A better fundamental grasp of tendon tissue biology is urgently required. This study will enable us to establish the role of matricellular protein SPARC in tendon function, thus enhance the understanding of tendon biology and enable translation of the bench work to potential clinical applications.
The Role Of Perlecan In Tensional Connective Tissues
Funder
National Health and Medical Research Council
Funding Amount
$605,037.00
Summary
Musculoskeletal diseases affect tension and weight bearing connective tissues which have notoriously poor repair capabilities. These conditions are difficult to treat clinically and surgical repair in many cases does not provide a return to optimal joint function impinging on the quality of life of afflicted individuals and their carers. Our project aims to better understand the structure and function of these tissues in health and disease with a view to improving repair strategies.
Tissue Engineering Approach To Musculoskeletal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Over the next few decades there is an anticipated steady increase in surgical intervention for bone, cartilage and tendon damages due to trauma or osteoporosis as a consequence of an aging population. These damages cause chronic pain, immobility, restricted activities, and, sometimes, death and are a considerable financial burden to the Australian Health System.
Pathobiology Of The Small Leucine Rich Repeat Proteoglycans In Cartilage, Intervertebral Disc And Tendon Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$516,625.00
Summary
Back problems (M$700), OA (M$600), muscle and tendon disorders (M$500) accounted for 60% of musculoskeletal (MSK) health care expenditure in Australia in 1993-1994, were the second most common cause of presentations to a general practitioner, the third leading contributor to health system expenditure (>$3 billion) and accounted for ~300,000 hospital admissions, ~15 million medical services and over 13 million prescriptions. Significant disability due to MSK disease were noted in ~50% of peopl ....Back problems (M$700), OA (M$600), muscle and tendon disorders (M$500) accounted for 60% of musculoskeletal (MSK) health care expenditure in Australia in 1993-1994, were the second most common cause of presentations to a general practitioner, the third leading contributor to health system expenditure (>$3 billion) and accounted for ~300,000 hospital admissions, ~15 million medical services and over 13 million prescriptions. Significant disability due to MSK disease were noted in ~50% of people aged 65 years. Australian census data indicates that ageing trends will result in an increased incidence of MSK conditions as the longevity of the Australian population rises, exerting an ever increasing burden on the healthcare budget. Extreme levels of sporting or physical activity from traumatic loading of joints can lead to excessive loading of collagen fibres in MSK tissues leading to their failure and loss of tissue function. Common end stages of collagen fibre breakdown are preceded by matrix changes which may predispose MSK tissues to enzymatic and mechanical damage. One such change is an increased degradation of a family of small leucine-rich proteoglycans (SLRPs) which modulate the diameter, strength and assembly of collagen fibrils and bind and modify the effects of reparative growth factors and degradative cytokines within connective tissues. Altered synthesis of SLRPs and SLRP fragments have been identified in abnormal intervertebral disc, cartilage and tendon. Very little is known however about how these fragments are generated within these tissues and how they affect growth factor binding or collagen fibril formation. This deficiency will be addressed in our proposed study which will provide novel information on mechanisms of cartilage, intervertebral disc and tendon degeneration and potential therapeutic and diagnostic targets which may be exploited in future studies on the treatment of these musculoskeletal conditions.Read moreRead less
Muscle Contracture In Multiple Sclerosis Prevalence And Rehabilitation
Funder
National Health and Medical Research Council
Funding Amount
$175,583.00
Summary
A population-based study of prevalence of muscle contracture will provide helpful information to health providers about the magnitude of the problem of contracture. This information will focus research efforts, and help health care providers to allocate resources appropriately. Recent studies have found that current treatments for contracture often provide transient or no effects. This project will test a promising new direction in treatment of contracture in people with multiple sclerosis.