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.
Experimental And Computational Study On Biomechanical Behavior Of Osteocytes
Funder
National Health and Medical Research Council
Funding Amount
$86,073.00
Summary
The experimental and computational methods (finite element method) are used to predict biomechanical behaviors of osteocytes under normal physiological loading, overloading or under-loading/disuse. This quantitative research will not only help to elucidate the mechanisms of mechanotransduction in osteocytes, it will provide important information that is also relevant to mechanobiology in general.
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.
Regulation Of Bone Resorption And Formation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,596,183.00
Summary
Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. ....Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. Osteoporosis results from an excess of bone breakdown over formation, and our Program aims to identify the factors that regulate these processes, and develop new therapies that can modify them. We will also determine what it is about bone cell properties that make some cancers, especially those of breast and prostate, particularly prone to spread to bone.Read moreRead less
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
Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased susceptibility to fractures. Understanding the nature of bone loss may lead to the discovery of a new drug target for the treatment of osteoporosis..
Factors That Affect Knee Structure In Healthy Women
Funder
National Health and Medical Research Council
Funding Amount
$199,176.00
Summary
Osteoarthritis (OA) has the largest impact of any chronic disease on burden of disease borne in later life, affecting women more often than men. The importance of OA has been acknowledged by its listing within musculoskeletal disease, the 7th health priority in Australia. It is 4 times as common in women as in men.Treatments which slow or prevent OA progressing are limited, so prevention must play a key role. With increasing disease severity, joint cartilage is lost. We have recently developed a ....Osteoarthritis (OA) has the largest impact of any chronic disease on burden of disease borne in later life, affecting women more often than men. The importance of OA has been acknowledged by its listing within musculoskeletal disease, the 7th health priority in Australia. It is 4 times as common in women as in men.Treatments which slow or prevent OA progressing are limited, so prevention must play a key role. With increasing disease severity, joint cartilage is lost. We have recently developed a method to measure joint cartilage from magnetic resonance imaging (MRI) scans which is able to assess the severity of structural changes in the knee. Using this method will allow us to assess 2 issues: 1) Obesity is the only identified modifiable risk factor for knee OA. However, the mechanism is poorly understood. Weight loss programs may be more effective at reducing the risk of OA if they are combined with programs aimed at maintaining muscle mass. 2) Bone is important in development of Knee OA, but its role is poorly understood. Understanding how bone metabolism relates to risk of knee OA may allow us to prevent disease. Bone is more likely to respond to pharmacological manipulation than cartilage. Thus it may prove a more effective target for intervention than cartilage. The Geelong Osteoporosis Study was begun in 1994 to study bone health in Australian women (urban and rural). Much information relevant to the risk of OA has been collected over the past decade. By performing MRI of the knee now and in 2 years time, we will determine the effect of different measures of obesity and bone metabolism on structural change at the knee which predisposes to OA. Since both of these factors (obesity and bone metabolism) are potentially modifiable, this study may offer new avenues of prevention and therapy in knee OA. This has the potential to promote a better quality of life as people age and to reduce the economic burden of knee OA in the community.Read moreRead less