GLUCOCORTICOID EFFECTS ON BONE: THE ROLE OF THE OSTEOBLAST
Funder
National Health and Medical Research Council
Funding Amount
$464,520.00
Summary
Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, ca ....Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, cartilage and skin, causing osteoporosis, muscle wasting and skin damage. As a matter of fact, cortisone-induced muscle and bone disease is one of the most frequent and serious side effects associated with glucocorticoid treatment, and substantially affects quality of life and co-morbidity in many patients. In the present project, we aim to develop new strategies for the understanding and prevention of costisone-induced bone disease. The first step is to investigate the mechanisms of actions of glucocorticoids in bone. To this aim, we have generated a model in which a cortisone- inactivating enzyme is produced in excess in the bone forming cells (osteoblasts). Previous studies have shown that these cells are protected against the effects on cortisone, while other cells not producing this enzyme remained vulnerable. We now intend to use this model to study the mechanisms of glucocorticoid action on bone and muscle under normal and diseased conditions (e.g. in a model of glucocorticoid excess and in a model of rheumatoid arthritis). We also intend to study how internal glucocorticoids affect the development of bone forming cells. Our long-term aim is to uncover new ways to target drug action to the desired tissues and cells, while protecting other tissues and cells from deleterious side effects.Read moreRead less
Identification Of The Mechanisms Of Lipotoxicity Within The Bone Marrow Milieu
Funder
National Health and Medical Research Council
Funding Amount
$416,007.00
Summary
Obesity and osteoporosis two major epidemics of our time. Bone and fat communicate with each other in two different ways. A hormonal communication links bone and fat in a positive manner. In contrast, at the local level, increasing levels of marrow fat with aging affect bone quality through the local release of toxic factors. We will identify these factors and will assess the potential reversibility of lipotoxicity in bone, as a new therapeutic approach to osteoporosis in the elderly.
Biothermosetting Bone Filler: An Injectable Osteoconductive Repair Material
Funder
National Health and Medical Research Council
Funding Amount
$601,698.00
Summary
Bone injury is a common and profoundly debilitating issue, and is responsible for extended partial or complete loss of mobility and associated economic impact during slow healing. There is strong demand for technology that reduces the time taken for bone repair. There is still a paucity of clinically effective biocompatible materials for treatment. We have developed a novel approach for a thermoresponsive hydrogel with unique properties suitable for rapid bone filling and regeneration.
Preclinical Optimisation Of Intrauterine Transplantation Of Fetal Mesenchymal Stem Cells For Osteogenesis Imperfecta.
Funder
National Health and Medical Research Council
Funding Amount
$600,932.00
Summary
Osteogenesis imperfecta is a genetic disorder causing brittle bones and fractures. Currently there is no good treatment. Transplanting stem cells before birth should allow them to build healthy bones early in life. Despite promising effects in animals, stem cell uptake is too low to prevent all fractures and ameliorate pain and deformity. We are studying how to improve the uptake of stem cells given to the fetus and neonate, in order to develop a treatment suitable for eventual use in humans.
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