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.
Regulation Of Bone Resorption In Periodontal Disease
Funder
National Health and Medical Research Council
Funding Amount
$258,500.00
Summary
Periodontal disease is the most common disease involving bone loss in the world. We know little about the causes and how the disease develops. Some of the bacteria that live in the mouth are associated with the disease but the presence of these bacteria does not mean a person will have it. We do not know why some people suffer from the disease and others do not. Unfortunately when a person has periodontal disease the dentist has few choices in the way in which the patient is treated. There are n ....Periodontal disease is the most common disease involving bone loss in the world. We know little about the causes and how the disease develops. Some of the bacteria that live in the mouth are associated with the disease but the presence of these bacteria does not mean a person will have it. We do not know why some people suffer from the disease and others do not. Unfortunately when a person has periodontal disease the dentist has few choices in the way in which the patient is treated. There are no drugs presently available to treat this disease and surgical removal of the diseased tissue is the only option for treatment. Often after this treatment the disease continues to get worse and more bone is lost sometimes resulting in the loss of teeth. This study aims to understand how the disease causes the bone loss. We believe that some newly identified factors that regulate the cells which destroy bone are responsible. Our recently works show that these factors are present in abnormal levels in the diseased tissues of patients. We also wish to go further and try and find ways of treating the disease. We aim to find new treatments based on controlling the factors that regulate the cells that destroy bone .Read moreRead less
Destructive bone loss is a serious complication of many common inflammatory diseases. Three important examples are are, periodontal disease, rheumatoid arthritis and peri-implant osteolysis. The mechanism of osteoclast formation in these diseases is distinctly different from physiologic osteoclast formation. Despite the prevalence of these diseases until recently little is known about how bone erosion occurs However, recent advances in the understanding of these diseases has allow us to better i ....Destructive bone loss is a serious complication of many common inflammatory diseases. Three important examples are are, periodontal disease, rheumatoid arthritis and peri-implant osteolysis. The mechanism of osteoclast formation in these diseases is distinctly different from physiologic osteoclast formation. Despite the prevalence of these diseases until recently little is known about how bone erosion occurs However, recent advances in the understanding of these diseases has allow us to better investigate the mechanisms of the bone loss. Drugs to stop the loss of bone have only recently been available to patients and many new treatments are being developed. While most of these drugs are proving useful to treat osteoporosis, their suitability for the treatment of bone loss in diseases such as periodontal disease, rheumatoid arthritis and peri-implant osteolysis is largely unknown. As the way bone is lost in these inflammatory diseases quite different from osteoporosis different treatments are needed. This project aims to better understand bone loss in these diseases and identify new treatments to prevent the debilitating bone loss associated with inflammation in disease.Read moreRead less
The Role Of V-ATPase Accessory Subunit Ac45 In Osteoclasts
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Osteoclasts are directly related to many lytic bone disorders including osteoporosis, osteoarthritis and Paget's diseases. Development of strategies to control the formation or activities of osteoclasts has been a major focus of bone research. The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is responsible for creating a low pH environment critical for bone resorption, and therefore a potential molecular target for the discovery of novel bone antiresorptive ag ....Osteoclasts are directly related to many lytic bone disorders including osteoporosis, osteoarthritis and Paget's diseases. Development of strategies to control the formation or activities of osteoclasts has been a major focus of bone research. The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is responsible for creating a low pH environment critical for bone resorption, and therefore a potential molecular target for the discovery of novel bone antiresorptive agents useful for the treatment of lytic bone disorders. The proposed research will give considerable insight into the role of the both V-ATPase accessory subunit Ac45 and V-ATPase complex in osteoclasts. Understanding the molecular and cellular mechanisms by which V-ATPases regulate osteoclast bone resorption will facilitate the development of novel and selective inhibitors for the treatment of lytic bone disorders.Read moreRead less
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
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
Breast Cancer has a particular preference to form cancer metastases in bone where its presence is associated with bone destruction that frequently results in significant pain and disability. Bone seems to provide a fertile soil for breast cancer cells that have moved into the blood vessels from the original cancer site in the breast. Once tumour cells have invade bone marrow spaces from the blood vessels they are able to grow and induce the normal cells of the bone marrow to destroy the surround ....Breast Cancer has a particular preference to form cancer metastases in bone where its presence is associated with bone destruction that frequently results in significant pain and disability. Bone seems to provide a fertile soil for breast cancer cells that have moved into the blood vessels from the original cancer site in the breast. Once tumour cells have invade bone marrow spaces from the blood vessels they are able to grow and induce the normal cells of the bone marrow to destroy the surrounding hard bone. This allows the tumour to grow faster. Together these processed create a vicious cycle that contributes to the serious consequences of bone metastases. In this project we will be studying mice with breast cancer to understand what makes the bone marrow such a fertile and receptive site for breast cancer metastasis. In particular, we are looking at how the normal processes of bone renewal and repair contribute to the establishment of cancer in bone. We will use the body's own bone protecting protein, called osteoprotegerin, to test how blocking bone destruction will affect the ability of cancer cells to invade and grow in bone. This study has the potential to change the way bone metastases are treated. Treatment of breast cancer could be significantly improved if the fertile soil of bone could be modified to either block the targeting of breast cancer to bone, or to inhibit its growth there.Read moreRead less