Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment an ....Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment and assessment of a cohort of 1500 postmenopausal women with either low or high bone mineral density from pre-existing population cohorts in Australia. A genomewide association study will then be performed on these cases. Associated genes in different datasets will then be investigated further in our cohort, and high-density SNP mapping performed to identify true associated variants. These studies should identify most genetic variants associated with BMD variation and low trauma fracture in the general community, allowing development of diagnostic-disease predictive genetic tests, and informing development of novel therapeutic agents for osteoporosis.Read moreRead less
Caltrin As A Calcium Transport Inhibitor During Osteoclastic Bone Resorption
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Excessive bone resorption has been observed in many common bone diseases such as osteoporosis, Paget's disease and arthritis. These are major health problems in Australia and other developed countries. Increased activation or formation of osteoclasts is responsible for the excessive bone resorption. Understanding the mechanisms by which the osteoclasts exert its function and activation is an important step toward developing strategies to combat excessive bone resorption for the treatment and pre ....Excessive bone resorption has been observed in many common bone diseases such as osteoporosis, Paget's disease and arthritis. These are major health problems in Australia and other developed countries. Increased activation or formation of osteoclasts is responsible for the excessive bone resorption. Understanding the mechanisms by which the osteoclasts exert its function and activation is an important step toward developing strategies to combat excessive bone resorption for the treatment and prevention of osteolytic disorders. This project attempts to address the important and fundamental issue of osteoclast function. We have identified caltrin, a known calcium transport inhibitor, that is likely to be biologically important in osteoclast calcium homeostasis. This project intends to investigate the role of caltrin in calcium-induced apoptosis, osteoclast bone resorption and the cellular and molecular mechanisms underlined. It will enhance our knowledge of calcium regulation in osteoclasts and provide information to facilitate the development of new anti-resorptive agents.Read moreRead less
The Role Of V-ATPase Accessory Subunit Ac45 In Osteoclasts
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Osteoclasts are directly related to many lytic bone disorders including osteoporosis, osteoarthritis and Paget's diseases. Development of strategies to control the formation or activities of osteoclasts has been a major focus of bone research. The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is responsible for creating a low pH environment critical for bone resorption, and therefore a potential molecular target for the discovery of novel bone antiresorptive ag ....Osteoclasts are directly related to many lytic bone disorders including osteoporosis, osteoarthritis and Paget's diseases. Development of strategies to control the formation or activities of osteoclasts has been a major focus of bone research. The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is responsible for creating a low pH environment critical for bone resorption, and therefore a potential molecular target for the discovery of novel bone antiresorptive agents useful for the treatment of lytic bone disorders. The proposed research will give considerable insight into the role of the both V-ATPase accessory subunit Ac45 and V-ATPase complex in osteoclasts. Understanding the molecular and cellular mechanisms by which V-ATPases regulate osteoclast bone resorption will facilitate the development of novel and selective inhibitors for the treatment of lytic bone disorders.Read moreRead less
The Role Of P62/A170 In Pathological Bone Destruction
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Approximately up to 30% of patients are admitted to public hospitals in Australia for reasons related to skeletal disorders, including trauma, osteoarthritis, osteoporosis, primary and secondary bone tumours, genetic and metabolic disorders. Abnormal bone resorption contributes to most of these diseases and conditions. Based on the clinical evidence of P62 mutation in patients with Paget's Disease of bone and our observation of the involvement of P62 in RANKL-induced NF-Kb signaling, we propose ....Approximately up to 30% of patients are admitted to public hospitals in Australia for reasons related to skeletal disorders, including trauma, osteoarthritis, osteoporosis, primary and secondary bone tumours, genetic and metabolic disorders. Abnormal bone resorption contributes to most of these diseases and conditions. Based on the clinical evidence of P62 mutation in patients with Paget's Disease of bone and our observation of the involvement of P62 in RANKL-induced NF-Kb signaling, we propose that intracellular molecule P62-A172 may play an important part in the switch off-on signals necessary for bone resorbing cells to resorb bone. To this end, we will study the molecular mechanism of P62 in action, and the interaction with its possible partners for the facilitation of abnormal bone resorption. The clinical significance of this project is to: 1) enhance understanding of abnormal bone resorption in Orthopaedic related diseases and conditions. 2) provide a strategy of drug development for the treatment of these disease and conditions.Read moreRead less
Determining The Function Of Parasite Proteins At The Membrane Skeleton Of Malaria-infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$392,036.00
Summary
Malaria is a serious disease that frequently kills its victim after a bout of high fever and coma. The most vicious form of malaria is caused by a minute parasite called Plasmodium falciparum that lives inside red blood cells. As these parasites grow, they make some dramatic renovations to their red blood cell home that make it become very stiff and sticky. Instead of flowing around the body like normal red blood cells, the infected cells become trapped in small veins and can no longer carry out ....Malaria is a serious disease that frequently kills its victim after a bout of high fever and coma. The most vicious form of malaria is caused by a minute parasite called Plasmodium falciparum that lives inside red blood cells. As these parasites grow, they make some dramatic renovations to their red blood cell home that make it become very stiff and sticky. Instead of flowing around the body like normal red blood cells, the infected cells become trapped in small veins and can no longer carry out their normal job. The ability of the parasite to make red blood cells stiff and sticky is what makes this type of malaria so dangerous, particularly when red cells get stuck in the brain. We plan to look at certain proteins that malaria parasites place on the walls of red blood cells because we think this is what makes them stiff and sticky. We hope this will help with the development of and urgently required ways to cure malaria.Read moreRead less