Artificial joint implants are widely used to replace diseased or damaged joints. Despite the impressive success of joint replacement many artificial joints do not last indefinitely. In many patients joints last for 25 years or more but in about 15% the artificial joints will fail prematurely. Artificial joints need to be replaced because of loosening resulting from the loss of bone from around the artificial joint. The bone loss is caused by large numbers of small particles generated by excessiv ....Artificial joint implants are widely used to replace diseased or damaged joints. Despite the impressive success of joint replacement many artificial joints do not last indefinitely. In many patients joints last for 25 years or more but in about 15% the artificial joints will fail prematurely. Artificial joints need to be replaced because of loosening resulting from the loss of bone from around the artificial joint. The bone loss is caused by large numbers of small particles generated by excessive wear of the artificial joint. We now know that specialised cells in the body react to the wear particles and try to destroy them. During this process they produce molecules which lead to bone destruction. This project seeks to investigate the way particles cause bone loss and to develop drug treatments that will either prevent the loss of bone or promote new bone to replace that which has been lost. The increasing use of joint replacement and an aging population means that the number of patients with artificial joint failure will increase. This will mean that an increasing amount of medical recourses will be needed to replace failed and painful artificial joints. It is planned that the findings obtained from this project will eventually result in drug treatments which can reduce the need for the replacement of artificial joints.Read moreRead less
Regulation Of Osteoclast Differentiation And Function By The PKC Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$424,189.00
Summary
Developing strategies to control the formation of osteoclasts which underlines many disorders such as osteoporosis and osteoarthritis has been a major focus of bone research.The proposed research examines the fundamental role of Protein Kinase C (PKC) in bone resorption.This work will help elucidate the role of PKC in osteoclast formation;define the physiological role of PKC in bone structure and bone resorption in vivo and develop the treatment of bone disorders.
Interaction Of Rab3D And Tctex-1 Is Required For Bone Resorption Through The Regulation Of Post-TGN Vesicle Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$391,510.00
Summary
Osteoclasts are multinucleated cells responsible for the breakdown-resorption of bone tissue. Elevated osteoclast numbers and-or activities is a major hallmark of a number of debilitating Orthopaedic-related diseases including osteoporosis, arthritis, bone cancer and aseptic loosening. Among these, osteoporosis is endemic in Western society with an estimated 1 in 2 women and 1 in 3 men sustaining a fracture in their lifetime. It is well accepted that the transport of carrier vesicles containing ....Osteoclasts are multinucleated cells responsible for the breakdown-resorption of bone tissue. Elevated osteoclast numbers and-or activities is a major hallmark of a number of debilitating Orthopaedic-related diseases including osteoporosis, arthritis, bone cancer and aseptic loosening. Among these, osteoporosis is endemic in Western society with an estimated 1 in 2 women and 1 in 3 men sustaining a fracture in their lifetime. It is well accepted that the transport of carrier vesicles containing bone destructive enzymes is critical for bone resorption by osteoclasts. Although vesicle transport has been shown to be associated with microtubules (the cells skeleton), the molecular mechanisms responsible for vesicle and microtubule interaction are largely unknown. We have identified a novel interaction between Rab3D, a vesicle transport molecule, with Tctex-1, a microtubule-binding protein. We propose that the binding of Rab3D to Tctex-1 in osteoclasts is essential for the interaction of vesicles with microtubules and, hence, osteoclast function. The focus of this project is to further confirm our hypothesis by analysing the importance of this interaction in osteoclast-mediated bone resorption. The anticpated outcomes of the proposed project are: 1) Rab3D-mediated vesicle transport is directed via the microtubule network; 2) Interaction between Rab3D and Tctex-1 is cruical for the coupling of Rab3D-mediated vesicle transport to the microtubules; and 3)Disruption of the Rab3D-Tctex-1 interaction may impair bone resorption. Understanding the molecular mechanisms which regulate osteoclastic vesicle trafficking might therefore enable us to develop new strategies to specifically target and inhibit breakdown of bone tissue.Read moreRead less
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.
A Randomised Controlled Trial Examining Stability Of New Types Of Highly Porous Surfaced Acetabular Components In Total Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$216,490.00
Summary
Numbers of total hip replacements are steadily increasing. The most common complication of hip replacement is late implant loosening, which can be predicted by early migration. We will examine early migration of a trabecular metal acetabular cup without screws, compared to a titanium fibre metal acetabular cup fixed with screws. Ideally, an acetabular cup would achieve a level of initial stability by press-fit alone without screws, as screws increase the risk of bone loss around the prosthesis.
The Interaction Of Ac45 With V-ATPase And Its Function In Osteoclastic Bone Resorption
Funder
National Health and Medical Research Council
Funding Amount
$671,613.00
Summary
Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and increased susceptibility to fractures. Of concern is osteoporotic fractures in the elderly are linked with increased mortality rates. Also, diseases associated with excess bone resorption place significant financial burden on the health care systems. We will examine the role of proton pump in bone resorption as a potential target for the treatment of osteoporosis.
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.