The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.
We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less
How common and what is the significance of cis-acting regulatory variation and genomic imprinting in plants? Plant based processes provide truly sustainable solutions to many of the challenges facing Australia. The proposed research will help elucidate how plants regulate variation in gene expression rather than changes in the structure of encoded proteins. This is an area of gene expression, that has not been approached before, that explains the plant's ability to respond to external stimuli. ....How common and what is the significance of cis-acting regulatory variation and genomic imprinting in plants? Plant based processes provide truly sustainable solutions to many of the challenges facing Australia. The proposed research will help elucidate how plants regulate variation in gene expression rather than changes in the structure of encoded proteins. This is an area of gene expression, that has not been approached before, that explains the plant's ability to respond to external stimuli. Variation between plant species in the number of genes does not fully explain the differences between them. This information will come not from seqenceing genomes but from investigation of regulatory elements. Read moreRead less
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
Regulation of Cellulose Biosynthesis in Commercially Important Cereal Crop Species. The long term strategic research alliance with DuPont Pioneer will lead to the development of breakthrough science in emerging technologies that are relevant: a) to agricultural production, b) to human health and c) to renewable bio-fuel production from crop residues. The alliance will attract significant international investment in Australian research and foster an intellectual environment for world-class resear ....Regulation of Cellulose Biosynthesis in Commercially Important Cereal Crop Species. The long term strategic research alliance with DuPont Pioneer will lead to the development of breakthrough science in emerging technologies that are relevant: a) to agricultural production, b) to human health and c) to renewable bio-fuel production from crop residues. The alliance will attract significant international investment in Australian research and foster an intellectual environment for world-class research training of postgraduate students and postdoctoral scientists, in both a higher education and an industry context.Read moreRead less
Identifying the diversity and evolution of loci associated with adaptation to aridity/heat and salinity in ancient cereal crops. This project will use ancient grains of wheat, barley and rye to find 'lost' genetic diversity at key genes associated with resistance to aridity, salt and disease. This project will make the proteins of key genes, and study their interaction with the environment over time by measuring ions in the grains to reveal the ancient environmental conditions.
Effects Of The Fatty Acid, Lauric Acid, On Energy Intake And Gut Motor And Hormonal Function In Health And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$744,645.00
Summary
Obesity is largely due to energy intake exceeding energy expenditure, thus, strategies that reduce energy intake will result in weight loss. We discovered recently that the fatty acid, lauric acid, markedly reduces energy intake. Our studies will determine the effects of lauric acid on energy intake and body weight reduction in obese subjects. The research is a new initiative and explores the potential of lauric acid as a novel, nutrient-based and side-effect free approach to obesity management.
Enhancing Genomic Prediction for Changing Environments in Wheat. Adverse weather is the primary risk faced by the Australian agriculture industry. This Project aims to develop the next generation of agriculture tools to unlock natural potential in wheat and improve yield stability across seasons and regions. Drawing on crop physiology, genetics and integrated modelling, this Project expects to generate new knowledge and technologies to untangle genetic and environmental interactions that affect ....Enhancing Genomic Prediction for Changing Environments in Wheat. Adverse weather is the primary risk faced by the Australian agriculture industry. This Project aims to develop the next generation of agriculture tools to unlock natural potential in wheat and improve yield stability across seasons and regions. Drawing on crop physiology, genetics and integrated modelling, this Project expects to generate new knowledge and technologies to untangle genetic and environmental interactions that affect productivity, enhance predictive capability, and initiate advanced breeding strategies to develop new crop varieties with superior resilience against changing climates. This should provide significant benefits, such as profit stability for wheat growers, elevated global market position and improved food security.Read moreRead less
Developing Zn-dense, high-yielding wheat by molecular marker technology. The objective of this project is to identify pathways leading to the accumulation of zinc — an important element for human nutrition — in wheat. The project aims to provide biochemical and molecular markers for breeding programs that will facilitate the selection of superior breeding lines for improved human nutrition and seed health. This project builds on studies using a wheat diversity panel with 90 000 gene-based single ....Developing Zn-dense, high-yielding wheat by molecular marker technology. The objective of this project is to identify pathways leading to the accumulation of zinc — an important element for human nutrition — in wheat. The project aims to provide biochemical and molecular markers for breeding programs that will facilitate the selection of superior breeding lines for improved human nutrition and seed health. This project builds on studies using a wheat diversity panel with 90 000 gene-based single nucleotide polymorphism (SNP) markers, where zinc–SNP associations were identified. The project also builds on recent studies that show particular metabolites and macronutrients around anthesis are linked to improved grain zinc concentration at maturity.Read moreRead less
Understanding the molecular mechanisms of intellectual disability. Intellectual disability is frequent in the population, with one in every fifty people in the world directly affected. This project will improve our understanding of the correct development and function of the brain required for cognition by investigating specific roles and regulation of key molecules involved.