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.
HARNESSING THE PHYSIOLOGICAL EFFECTS OF STRONTIUM AND ZINC TO PRODUCE NOVEL BIOMATERIALS FOR ORTHOPAEDIC APPLICATIONS
Funder
National Health and Medical Research Council
Funding Amount
$560,082.00
Summary
Large skeletal defects resulting from congenital defects or disease processes are challenging to regenerate and represent a major financial burden to our health system. Bone graft treatments are widely used but have considerable drawbacks. Available synthetic alternatives lack the physical-biological properties necessary. We have developed new scaffolds with improved mechanical-biological properties for bone regeneration.
Mechanisms Of Bone Formation At The Device/tissue Interface: Role Of Biomaterial Surface Chemistry Modification
Funder
National Health and Medical Research Council
Funding Amount
$489,375.00
Summary
In 1992 300,000 prosthetic devices, artificial hips and knees were implanted into patients in a global market worth $2.1 billion. Growth in this field of medicine has been exceptional with now more than 1 million implants carried out each year. In 1998-99, 38,512 artificial hips and knees were implanted in Australia alone, with approximately 10% of these replacing older, failed implants. Since joint replacements provide great benefits for the patient considerable health funding is required for j ....In 1992 300,000 prosthetic devices, artificial hips and knees were implanted into patients in a global market worth $2.1 billion. Growth in this field of medicine has been exceptional with now more than 1 million implants carried out each year. In 1998-99, 38,512 artificial hips and knees were implanted in Australia alone, with approximately 10% of these replacing older, failed implants. Since joint replacements provide great benefits for the patient considerable health funding is required for joint replacements. However, failure of the implants is a major concern to the patient and financially to our health system, especially with the ever increasing life expectancy of our population. The long-and short-term success of an implant depends on the healthy support of the surrounding bone. This study aims to find ways of improving the attachment of healthy bone to the implant by modifying the surface characteristics of the implant. We will modify the surface chemistry of biomaterials with divalent cations, such as magnesium, which is known to play a critical role in bone remodelling and skeletal development. Our goal is to improve the formation of healthy bone that will promote a rapid and permanent fixation of implant into skeletons. This study goes further to study the factors, inside the cell, on the cell surface and secreted by the cell, which promote this attachment. Once these factors are identified, it should be possible to alter implant surfaces in ways to improve stability. In this proposal we will use novel bioceramic coatings and ion beam technologies. This study will not only improve our understanding of the interactions of bone and implant but also identify ways of improving implants to benefit the patient's quality of life and reduce costs in this important heath areaRead moreRead less
At present the failure rate of joint replacement is unacceptably high and will continue to rise due to the ageing and active life styles of the baby-boomer generation, placing an increasing burden on the health budget. We have developed a new bioactive material with improved mechanical-biological properties for bone regeneration. We will modify the surface of the currently used orthopaedic implants with this bioactive material to promote permanent fixation of the prosthesis to the bone.
Role Of Lamin A-C In Osteoblastogenesis And Age-related Bone Loss
Funder
National Health and Medical Research Council
Funding Amount
$475,515.00
Summary
Osteoporosis prevalence in Australia has increased, especially in the older population. Patients with accelerated aging (Hutchinson Gilford) suffer from severe osteoporosis. A mutation in lamin A-C was identified as the cause of this disease. Therefore it could be the link between aging and bone loss. We will identify the role of lamin in bone biology. We will generate a new understanding of the connection between aging and bone loss and a new potential therapeutic target for senile osteoporosis
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 Endogenous Glucocorticoids In Autoimmune Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$693,185.00
Summary
Inflammatory joint diseases affect millions of people worldwide and in most patients these often chronic conditions can not be cured. In an experimental model of arthritis we have found that bone cells can modify the severity of inflammation when certain hormonal signals are blocked. This study will identify the mechanisms underlying these hormonal effects with the aim to find new targets for efficient treatments for arthritis.
There are a number of important medical conditions that are characterised by a loss of bone. These include osteoporosis, cancer-induced bone loss, and the bone loss that causes loosening of orthopaedic prostheses. Bone loss is understood to be due to an excess of bone resorption by osteoclasts in relation to bone formation. Understanding of the regulation of osteoclast formation and activity has increased greatly in the last few years, but important questions remain. In particular, more informat ....There are a number of important medical conditions that are characterised by a loss of bone. These include osteoporosis, cancer-induced bone loss, and the bone loss that causes loosening of orthopaedic prostheses. Bone loss is understood to be due to an excess of bone resorption by osteoclasts in relation to bone formation. Understanding of the regulation of osteoclast formation and activity has increased greatly in the last few years, but important questions remain. In particular, more information is needed about the process of human osteoclast formation. We have devised a novel cell culture model of human osteoclast formation, in which osteoclast precursor cells mature into osteoclasts under the influence of human osteoblast cells. The importance of this model is that it allows us, for the first time, to investigate the role, and the potential relevance in human disease, of agents that positively and negatively affect osteoclasts. We intend also to use this model to study the way in which cancer cells in bone cause bone loss, as well as the involvement of cells of the immune system in osteoclast formation, in normal bone and in inflammatory conditions.Read moreRead less