Determining The Influences Of Cell Stress And Heat Shock Factor-1 Action In Osteoclast Formation And Pathological Bone Loss.
Funder
National Health and Medical Research Council
Funding Amount
$657,287.00
Summary
Cancer and rheumatoid arthritis cause painful bone destruction. This occurs due to increased numbers of bone destroying cells called osteoclasts. We found stress responses in bone cells can increase osteoclast numbers by activating proteins inside the bone cells that encourage osteoclasts to form. We will thus study whether cell stress blocking drugs might stop bone loss. As arthritis and cancer both cause stress responses, this work could identify a new way that such diseases affect bone.
Molecular Mechanisms Of Joint Degeneration In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$718,273.00
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 for explore the role of a new regulator of gene expression, microRNA, in the initation and progression of osteoarthritis. This will provide important new information on disease mechanisms for the development of diagnostic biomarkers and therapies
Modulation Of Osteoclast Formation And Function To Prevent Joint Destruction In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$443,250.00
Summary
Rheumatoid arthritis is a disease that affects about 200,000 Australians. It is characterised by painful joint destruction leading to work disability, diminished quality of life and decreased life expectancy. The usual treatment of arthritis leads to less inflammation however it cannot be relied upon to control bone and joint destruction. Patients often have long term worsening of joint function despite short and medium term improvement in joint pain and swelling. One reason for this paradox may ....Rheumatoid arthritis is a disease that affects about 200,000 Australians. It is characterised by painful joint destruction leading to work disability, diminished quality of life and decreased life expectancy. The usual treatment of arthritis leads to less inflammation however it cannot be relied upon to control bone and joint destruction. Patients often have long term worsening of joint function despite short and medium term improvement in joint pain and swelling. One reason for this paradox may be that while research has mainly focused on inflammation, far less is known about the processes responsible for bone damage. Normally, specialised bone cells called osteoclasts carry out bone breakdown during growth and maintenance of the skeleton. In rheumatoid arthritis, these cells are responsible for the joint damage; this proposal, therefore, focuses on inhibiting the activity of these cells as a new therapy. So far, our work using a model of human rheumatoid arthritis has demonstrated that it is possible to separate joint inflammation from joint damage by selectively targeting osteoclasts with an inhibitor known as Osteoprotegerin. Besides Osteoprotegerin, we have identified two novel molecules named OCIL and sFRP-1 and shown that they are present in the joints of animals and humans with arthritis. Very recent experiments in our laboratory show that in the test tube, OCIL and sFRP-1 (like Osteoprotegerin) block osteoclast activity. The sFRP-1 molecule may also block a very important messenger molecule in arthritis called tumour necrosis factor. We therefore propose to study the effect of OCIL and sFRP-1 in the joints of mice with arthritis. We expect that these new inhibitors will have favorable effects on joint damage. If so, they could undergo further testing for use in humans. We believe that investigations along these lines may provide a rationale for an entirely new treatment approach to improve the long term outcome for patients with arthritis.Read moreRead less
Characterization Of Casein Phosphopeptide Amorphous Calcium Fluoride Phosphate As A Remineralization System
Funder
National Health and Medical Research Council
Funding Amount
$493,514.00
Summary
Dental caries (tooth decay) remains a major public health problem in Australia with an economic burden in excess of $1 billion p.a. The overall aim of this project is the development of a novel remineralizing agent (casein phosphopeptide stabilized amorphous calcium fluoride phosphate) for the remineralization of early tooth decay lesions (white spot lesions). The project will involve the testing of the ability of the novel remineralization system to remineralize (repair) white spot lesions in v ....Dental caries (tooth decay) remains a major public health problem in Australia with an economic burden in excess of $1 billion p.a. The overall aim of this project is the development of a novel remineralizing agent (casein phosphopeptide stabilized amorphous calcium fluoride phosphate) for the remineralization of early tooth decay lesions (white spot lesions). The project will involve the testing of the ability of the novel remineralization system to remineralize (repair) white spot lesions in vitro and in situ. The project also involves the detailed characterization of the molecular interactions of the components of the remineralizing system using NMR spectroscopy and other techniques. It is anticipated that this project will result in the development of a system with substantialy superior properties for the non-invasive treatment (reversal) of white spot lesions and may ultimately lead to the development of a novel system for the treatment and prevention of tooth decay.Read moreRead less
Enhanced Enamel Remineralisation With CPP-ACP And Fluoride
Funder
National Health and Medical Research Council
Funding Amount
$668,074.00
Summary
Tooth decay remains a major public health problem. The project will involve the testing of the system to remineralize (repair) early stages of decay in the laboratory. The project also involves the detailed characterization of the molecular interactions of the components of a system. It is anticipated that this project will result in the development of a system with substantialy superior properties for the non-invasive treatment (repair) of early tooth decay.