Furin: Carving-up Vital Substrates For Bone Remodelling And Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$815,972.00
Summary
Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures. It is caused by an imbalance between the cells that are constantly reabsorbing and reforming bone. The proposed project will address furin as a novel regulator of bone remodelling.
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.
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.
Heat Shock Transcription Factors In Bone Remodeling And Disease
Funder
National Health and Medical Research Council
Funding Amount
$480,427.00
Summary
The denisity of bone is finely balaned and required for a healthy lifestyle. During times of disease, damage or drug treatments the bone can be compromised, often decreasing in density and becoming fragile. This often leads to fractures, pain and a poor quality of life. This proposal seeks to investigate whether stress insults to bones plays a role in the loss of bone. This will provide new insights into bone loss during disease and lead to novel treatment strategies.
Relationships Between Human Osteoblasts And Haemopoietic Cells In Bone Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$436,450.00
Summary
Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collabora ....Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collaboration between osteoblasts and osteoclasts. Osteoblasts stimulate the formation of osteoclasts and also produce new bone at resporption sites. However, the way that the same type of cell can perform both these tasks, is not clear. Our studies are designed to increase our understanding of the development of human osteoblasts and of the factors that cause them to be sequentially pro-osteoclastic and then pro-osteogenic. We believe that an important factor in this process is vitamin D and we will test the hypothesis that this molecule is produced in bone and acts locally to regulate bone turnover.Read moreRead less
The Role Of CHKB In Osteoclastic Bone Resorption And Bone Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$565,695.00
Summary
Osteoporosis is a devastating disorder. Osteoporotic fractures in the elderly have been correlated with increased mortality rates. Osteoporosis alone costs $13.8 billion p.a. in USA and tens of millions of dollars in Australia. Cost to society of our ageing population for people become disabled by hip fractures alone could triple by the year 2040. Our research examines the role of CHKB in bone loss which may underscore its potential as a new molecular target for anti-resorptive drug development.
Role Of The Osteoclast In Endochondral Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$310,136.00
Summary
Failure of bone healing leads to significant pain and disability, such that augmentation of fracture repair is a dynamic and important field of study. A full understanding of bone repair is necessary before we can hope to introduce successful therapies. We theorise that by stimulating bone forming cells and inhibiting bone resorbing cells we may be able to provide optimal results. Bone resorbing cells, or osteoclasts, have long been considered essential to the initial stages of bone repair (endo ....Failure of bone healing leads to significant pain and disability, such that augmentation of fracture repair is a dynamic and important field of study. A full understanding of bone repair is necessary before we can hope to introduce successful therapies. We theorise that by stimulating bone forming cells and inhibiting bone resorbing cells we may be able to provide optimal results. Bone resorbing cells, or osteoclasts, have long been considered essential to the initial stages of bone repair (endochondral ossification) during which the early soft cartilaginous callus is replaced by hard mineralised callus. Our preliminary studies lead us to believe that endochondral ossification can indeed proceed without osteoclast activity. If we can safely eliminate osteoclast function early in the early stages of fracture repair, a number of therapeutic options open up for the augmentation of bone healing. The return of osteoclast function is necessary in the long term, so our strategy will also need to take this into account. This study will establish which systems are pivotal in endochondral ossification and therefore which interventions we should explore.Read moreRead less
Role Of Bone-associated Macrophages In Bone Remodelling And Bone Disease
Funder
National Health and Medical Research Council
Funding Amount
$564,963.00
Summary
Musculoskeletal diseases, including osteoporosis and osteoarthritis, are a national and international health and research priorities. Over 3 million Australians suffer from arthritis and musculoskeletal conditions and their social and economic impact is expected to dramatically increase in the next 20 years as a result of the aging population. Early diagnosis, prevention and treatment of many musculoskeletal diseases are currently inadequate. Consequently, there is a high demand for effective tr ....Musculoskeletal diseases, including osteoporosis and osteoarthritis, are a national and international health and research priorities. Over 3 million Australians suffer from arthritis and musculoskeletal conditions and their social and economic impact is expected to dramatically increase in the next 20 years as a result of the aging population. Early diagnosis, prevention and treatment of many musculoskeletal diseases are currently inadequate. Consequently, there is a high demand for effective treatment options. This project grant application proposes a novel line of scientific investigation that will provide greater understanding of the contribution of macrophages (a cell type that has important roles in normal tissue maintenance and defense against infection) in bone remodelling and disease. Bone is continuously remodelled and replaced to maintain skeletal strength and mineral metabolism. We have shown that a population of macrophages is intimately associated with bone and propose that these cells play an important part in regulating bone remodelling. Macrophages have been implicated in many diseases that have damaging consequences on bone, including osteoporosis and several forms of arthritis, linking aberrant macrophage function to disease-associated bone damage. This project aims to characterize this population of bone-associated macrophages and determine their ability to influence the function of other cells integrally involved in bone remodelling. We will also undertake studies in animal models to determine whether these cells are required for bone remodelling and-or damage. Detailed description of the novel role of macrophages in bone biology will facilitate the development of superior therapeutics, preventatives and cures for bone diseases.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