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.
Interaction Of Rab3D And Tctex-1 Is Required For Bone Resorption Through The Regulation Of Post-TGN Vesicle Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$391,510.00
Summary
Osteoclasts are multinucleated cells responsible for the breakdown-resorption of bone tissue. Elevated osteoclast numbers and-or activities is a major hallmark of a number of debilitating Orthopaedic-related diseases including osteoporosis, arthritis, bone cancer and aseptic loosening. Among these, osteoporosis is endemic in Western society with an estimated 1 in 2 women and 1 in 3 men sustaining a fracture in their lifetime. It is well accepted that the transport of carrier vesicles containing ....Osteoclasts are multinucleated cells responsible for the breakdown-resorption of bone tissue. Elevated osteoclast numbers and-or activities is a major hallmark of a number of debilitating Orthopaedic-related diseases including osteoporosis, arthritis, bone cancer and aseptic loosening. Among these, osteoporosis is endemic in Western society with an estimated 1 in 2 women and 1 in 3 men sustaining a fracture in their lifetime. It is well accepted that the transport of carrier vesicles containing bone destructive enzymes is critical for bone resorption by osteoclasts. Although vesicle transport has been shown to be associated with microtubules (the cells skeleton), the molecular mechanisms responsible for vesicle and microtubule interaction are largely unknown. We have identified a novel interaction between Rab3D, a vesicle transport molecule, with Tctex-1, a microtubule-binding protein. We propose that the binding of Rab3D to Tctex-1 in osteoclasts is essential for the interaction of vesicles with microtubules and, hence, osteoclast function. The focus of this project is to further confirm our hypothesis by analysing the importance of this interaction in osteoclast-mediated bone resorption. The anticpated outcomes of the proposed project are: 1) Rab3D-mediated vesicle transport is directed via the microtubule network; 2) Interaction between Rab3D and Tctex-1 is cruical for the coupling of Rab3D-mediated vesicle transport to the microtubules; and 3)Disruption of the Rab3D-Tctex-1 interaction may impair bone resorption. Understanding the molecular mechanisms which regulate osteoclastic vesicle trafficking might therefore enable us to develop new strategies to specifically target and inhibit breakdown of bone tissue.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
Effect Zoledronic Acid And Risedronate On The Preservation Of The Femoral Head In A Rat Model Of Perthes Disease
Funder
National Health and Medical Research Council
Funding Amount
$199,750.00
Summary
Perthes Disease (Legg-Perthes Disease) is a common childhood disorder, which leads to collapse and deformity of the growing hip joint. This can lead to arthritis in adult life, as well as a short leg on the affected side. The cause is as yet unknown. A class of drugs called bisphosphonates has been shown to help children with osteogenesis imperfecta (brittle bone disease). We believe, based on our extensive studies of the effect of these drugs on bone healing, that they could also help children ....Perthes Disease (Legg-Perthes Disease) is a common childhood disorder, which leads to collapse and deformity of the growing hip joint. This can lead to arthritis in adult life, as well as a short leg on the affected side. The cause is as yet unknown. A class of drugs called bisphosphonates has been shown to help children with osteogenesis imperfecta (brittle bone disease). We believe, based on our extensive studies of the effect of these drugs on bone healing, that they could also help children with Perthes disease. Although proving to be safe and effective in children with osteogenesis imperfecta, before exposing children with Perthes disease to the risk of any side effects, animal studies are needed. A certain type of rat called the spontaneously hypertensive rat gets a condition almost exactly the same as Perthes disease. This study will treat a large number of these rats and perform detailed study into whether it has a positive effect on preserving the shape of the hip joint, as well as looking into how this actually occurs. A successful outcome would pave the way for trials in children with Perthes disease, and could result in the avoidance of surgery and improved health outcomes for the children.Read moreRead less
The Australian Study Of Cost And Utilities Related To Osteoporotic Fractures
Funder
National Health and Medical Research Council
Funding Amount
$411,627.00
Summary
The research will quantify the cost and quality of life impact of fragility fractures in Australia. The study design is based on an international study - International Costs and Utilities Related to Osteoporotic Fracutres Study (ICUORS) that aims to investigate the impact of osteoporosis-related fractures of the hip, spine and wrist. Results can be used to compare cost-effectiveness of different drugs and lifestyle interventions aiming to decrease the burden of osteoporosis in Australia.
Artificial joint implants are widely used to replace diseased or damaged joints. Despite the impressive success of joint replacement many artificial joints do not last indefinitely. In many patients joints last for 25 years or more but in about 15% the artificial joints will fail prematurely. Artificial joints need to be replaced because of loosening resulting from the loss of bone from around the artificial joint. The bone loss is caused by large numbers of small particles generated by excessiv ....Artificial joint implants are widely used to replace diseased or damaged joints. Despite the impressive success of joint replacement many artificial joints do not last indefinitely. In many patients joints last for 25 years or more but in about 15% the artificial joints will fail prematurely. Artificial joints need to be replaced because of loosening resulting from the loss of bone from around the artificial joint. The bone loss is caused by large numbers of small particles generated by excessive wear of the artificial joint. We now know that specialised cells in the body react to the wear particles and try to destroy them. During this process they produce molecules which lead to bone destruction. This project seeks to investigate the way particles cause bone loss and to develop drug treatments that will either prevent the loss of bone or promote new bone to replace that which has been lost. The increasing use of joint replacement and an aging population means that the number of patients with artificial joint failure will increase. This will mean that an increasing amount of medical recourses will be needed to replace failed and painful artificial joints. It is planned that the findings obtained from this project will eventually result in drug treatments which can reduce the need for the replacement of artificial joints.Read moreRead less