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.
Molecular Characterization Of V-ATPase V0 Domain Subunits E1 And E2 In Osteoclast
Funder
National Health and Medical Research Council
Funding Amount
$558,909.00
Summary
Osteoporotic fractures in the elderly are often linked to increased mortality rates. Excess bone resorption is a major contributor to the onset of the disease. The proposed project focuses on the investigation of the molecular mechanisms of acid secretion that is required for the bone degradation in body. The project will examine the role of the proton pump in bone resorption and seek potential targets for the treatment of osteoporosis.
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.
The Role Of Muscle And The Application Of Muscle-cell Therapies In Bone Repair
Funder
National Health and Medical Research Council
Funding Amount
$438,936.00
Summary
Muscle is often close to bone and we have found that muscle cells can directly contribute to bone repair. We are examining importance of muscle cells in orthopaedic repair and whether new methods for mobilizing muscle cells can improve healing.
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.
Novel Therapeutic Interventions For The Orthopaedic Complications Of Neurofibromatosis Type 1 (NF1).
Funder
National Health and Medical Research Council
Funding Amount
$628,422.00
Summary
Children with the genetic disease NF1 can develop fractures that fail to unite and this can lead to amputation. We have advanced models of NF1-deficient bone cells and fracture healing that we will use to test new pharmaceutical treatments for NF1.
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.
Cell Biology Of Stress Fractures: Activation Of Remodelling At Sites Of Non-union
Funder
National Health and Medical Research Council
Funding Amount
$493,817.00
Summary
Stress fractures are debilitating injuries. We characterised a model of stress fractures in rat ulnae, learning that they heal by activated remodelling, that key genes are expressed in a temporal pattern, and that part of the fracture remains un-healed, similar to many clinical cases. Now, we will examine cell localisation of important genes necessary for remodelling, and test the efficacy of different growth factors to activate a healing response in the non-healed section of the fracture.