The Role Of 'Orphan' Transporters In Bone Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$675,668.00
Summary
Osteoclasts (OCs) are giant multinucleated cells exclusively responsible for physiological bone degradation (resorption). Excessive OC activity leads to localised bone destruction (osteolysis) as observed in patients with osteoarthritis and underlies decreased bone mass and fragility fractures that are a hallmark of osteoporosis. This project examines the role of an orphan solute carrier transporter in OC function and its potential involvement in bone disease.
Effect Of Lipid Mediators And Dietary Fats In Bone Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$380,250.00
Summary
Osteoporosis in a major public health problem which directly affects about 10% of the population, which is currently around 2 million Australians. With aging of the population, it is projected that this proportion will increase to more than 13% over the next 20 years. When it is considered that the direct hospital and residential care costs attributable to osteoporotic fractures currently approaches $2 billion per annum, low-cost interventions for increasing bone strength which are easily applie ....Osteoporosis in a major public health problem which directly affects about 10% of the population, which is currently around 2 million Australians. With aging of the population, it is projected that this proportion will increase to more than 13% over the next 20 years. When it is considered that the direct hospital and residential care costs attributable to osteoporotic fractures currently approaches $2 billion per annum, low-cost interventions for increasing bone strength which are easily applied to the elderly population have enormous potential for health benefits in Australia. Thus study will examine the effects of dietary omega-3 fats, of the kind found in fish and fish oil, on the biology of bone metabolism and on bone strength. The results will provide information which may be used in developing simple drug or dietary strategies for large-scale use for increasing bone mass and strength in the elderly population. A strength of the study arises from the combination of research expertise in (a) dietary fats, and (b) molecular biology of bone cells, and (c) animal models of bone metabolism which are amenable to dietary interventions. This combination is unique, but builds on well established systems which hitherto have existed in separate research paradigms. The Chief Investigator has considerable experience in development of diets enriched in omega-3 fats which are practical and suitable for daily use on a long-term basis. This adds considerably to the potential significance of the outcomes because, if favourable effects of omega-3 fats are observed and are characterised with regard to mechanisms, the results can be rapidly translated into large-scale clinical use.Read moreRead less
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.
gp130 is a protein expressed in all cells in the body; this project will analyse the influence of gp130 within the cells that form bone, the cells that destroy bone, and the cells that form a communication network within the bone matrix. Understanding the way this protein works will help us to understand how current therapies for osteoporosis work, and will help us to design new therapies.
Myo1b Bridges The Actin-membrane Interface During Osteoclastic Bone Resorption
Funder
National Health and Medical Research Council
Funding Amount
$429,387.00
Summary
Osteoporosis is a debilitating bone disease which features progressive bone loss. Bone loss (resorption) is driven by the bone resident cell the osteoclast. Identifying molecules that regulate bone resorption by osteoclasts is a crucial first step towards developing new targets for theraputic intervention. This proposal explores the role of Myo1b, a novel protein that appears to facilitate osteoclastic bone resorption and thus represents an attractive new candidate to target bone loss.
Molecular Mechanisms And Therapeutic Effects Of Novel Parthenolide Analogs On Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Rheumatoid arthritis and osteoporosis are common bone diseases with features of bone loss. Drugs that inhibit bone loss are needed for the prevention and treatment of bone diseases. The proposed research explores the potential use of novel herbal inhibitors for the suppression of bone resorbing cells, and their potential as treatments for bone loss.
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.
Relationship Of The Anabolic And Catabolic Responses In Healing A Critical Sized Defect In Rats
Funder
National Health and Medical Research Council
Funding Amount
$329,750.00
Summary
Delayed bone healing after trauma is a large clinical problem. Figures suggest up to 60,000 fractures result in a delay in healing in Australia per year. Bone healing can also fail to occur in other circumstances, such as after an operation. Research effort into new approaches to solving these problems is clearly justified. We believe that in some situations, bone healing fails due to the body's healing response, the anabolic response, being insufficient. In some other situations, the body's bon ....Delayed bone healing after trauma is a large clinical problem. Figures suggest up to 60,000 fractures result in a delay in healing in Australia per year. Bone healing can also fail to occur in other circumstances, such as after an operation. Research effort into new approaches to solving these problems is clearly justified. We believe that in some situations, bone healing fails due to the body's healing response, the anabolic response, being insufficient. In some other situations, the body's bone resorbing response, the catabolic response, may be too high and prevent healing from occurring. In normal bone healing, there is a balance between the anabolic and catabolic response. In disordered bone healing, these responses are out of balance. Several reasonably new treatments are available which can increase the anabolic response or decrease the catabolic response. We have preliminary results showing that with these agents we can bring these elements into better control, and thus drive bone healing. We have optimised an animal model where both the anabolic and catabolic responses can be controlled. In this project, we explore the optimisation of the timing and magnitude of anabolic and catabolic responses in bone healing.Read moreRead less
Fractures And Bisphosphonates: Reviving Osteoporosis Treatment Uptake By Identifying The Genetic, Material, And Microstructural Risk Factors Of Atypical Femur Fractures.
Funder
National Health and Medical Research Council
Funding Amount
$1,053,094.00
Summary
Atypical femoral fractures (AFF) are uncommon, but catastrophic, complications of antiresorptive osteoporosis treatments including bisphosphonates. We will identify patients at risk of AFF by determining changes in their bone structure and quality, and identifying genes that increase the risk of these fractures. In this way, cheap and effective antiresorptive treatments can be targeted to patients at the lowest risk of AFF and alternative treatments to those at highest risk.
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