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.
Osteal Macrophages As Therapeutic Targets For Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$618,015.00
Summary
Fragility fracture associated with osteoporosis is a substantial health problem costing $1.62 billion to treat in 2012 in Australia. There is no approved therapy to improve and accelerate fracture healing to help reduce this increasing health burden. This research will advance understanding of fracture repair in healthy and osteoporotic bone and progress development of a fracture therapy to improve bone repair by promoting specialised immune cells.
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
Short-term Use Of Intermittent PTH To Accelerate Healing Of Stress Fractures And During Bisphosphonate Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$633,331.00
Summary
Osteoporosis treatments prevent fractures by hindering cells that erode the skeleton. Normally, those cells also repair injuries like stress fractures. Some patients, treated for long periods, can suffer fractures because the treatment slows bone healing. We have an innovative model to test alternative treatments to accelerate stress fracture healing, while osteoporosis treatment continues. This could prevent unusual stress fractures, in patients who still need the bone-sparing effectiveness of ....Osteoporosis treatments prevent fractures by hindering cells that erode the skeleton. Normally, those cells also repair injuries like stress fractures. Some patients, treated for long periods, can suffer fractures because the treatment slows bone healing. We have an innovative model to test alternative treatments to accelerate stress fracture healing, while osteoporosis treatment continues. This could prevent unusual stress fractures, in patients who still need the bone-sparing effectiveness of osteoporosis treatment.Read moreRead less
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.
Sclerostin And Dickkopf-1 In Regulation Of Bone Mass
Funder
National Health and Medical Research Council
Funding Amount
$638,581.00
Summary
The WNT pathway is a powerful regulator of bone cell differentiation and bone formation. Two WNT modulators, sclerostin ad Dickkopf 1, are being developed for therapy in bone disease, but critical questions remain unanswered. In this study we use unique genetic mouse models created by the applicants to resolve specific deficiencies surrounding their actions and application as therapies.
NT-3 As An Upstream And Potentially Master Regulator Promoting Bone Fracture Healing
Funder
National Health and Medical Research Council
Funding Amount
$712,857.00
Summary
There is a strong clinical need for cost-effective treatments for delayed healing or non-union bone fractures. Our recent data suggest injury site-derived neurotrophin-3 (NT-3) may be an important overall regulator of bone repair by inducing key factors involved in fracture callus formation and remodelling. This project will address roles and mechanisms of endogenous NT-3 in bone repair and the likelihood of exogenous NT-3 protein in promoting bone healing in clinically relevant fracture models.
Osteal Macrophages: Novel Regulators Of Osteoblast Function And The Endosteal Stem Cell Niche
Funder
National Health and Medical Research Council
Funding Amount
$406,125.00
Summary
Bone diseases are a major health problem and current treatments are inadequate. We are investigating a novel role for macrophages (cells important in tissue maintenance and immune responses) in bone growth, repair and disease. Greater understanding of this will provide new ways to treat bone disease. We will also determine if these macrophages help support stem cells that reside near bone surfaces, which may provide new treatment strategies to improve bone marrow transplantation in cancer.