Prostaglandin G/H Synthase-2 (PGHS-2) Is A Key Regulator Of Skeletal Adaptation And Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$301,018.00
Summary
Knowledge of the biology underlying bone formation is important for developing novel approaches to stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for reducing inflammation, has considerable clinical significance. Specific inh ....Knowledge of the biology underlying bone formation is important for developing novel approaches to stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for reducing inflammation, has considerable clinical significance. Specific inhibition of PGHS-2 by recent anti-inflammatory drugs avoids formation of gastric ulcers, but their influence on normal bone remodelling and fracture repair is not known and must be investigated. Many such inhibitors are in advanced clinical trials, but their effect on bone metabolism has not been published. This project is important because it employs novel experimental models to advance our knowledge of prostaglandin biology in skeletal adaptation, and elucidates important clinical consequences for specific inhibition of PGHS-2 in the skeleton. This project will investigate the regulation of prostaglandin production by PGHS enzymes following mechanical loading in vivo. It will use cell, molecular and histochemical techniques to determine if the genes that regulate the enzymes are influenced by mechanical stimuli, and if they are dependent on other molecules, associated with structural proteins (stress fibres) within the cell. It will investigate if inhibition of PGHS-2 by antiinflammatory drugs or stress-fibre inhibitors, depresses normal bone turnover and healing responses. The outcome of these experiments could indicate new approaches to stimulate bone formation, preserve bone mass, or minimise adverse skeletal effects of anti-inflammatory treatments related to orthopaedic or dental procedures.Read moreRead less
Heat Shock Transcription Factors In Bone Remodeling And Disease
Funder
National Health and Medical Research Council
Funding Amount
$480,427.00
Summary
The denisity of bone is finely balaned and required for a healthy lifestyle. During times of disease, damage or drug treatments the bone can be compromised, often decreasing in density and becoming fragile. This often leads to fractures, pain and a poor quality of life. This proposal seeks to investigate whether stress insults to bones plays a role in the loss of bone. This will provide new insights into bone loss during disease and lead to novel treatment strategies.
Advanced micro-architecture and nanotopography for enhanced tissue growth in scaffolds. Tissue engineering scaffolds offer an urgently needed synthetic biomaterials solution to overcome disease transmission from donor transplants. This work will combine biomaterial chemistry and designed surface topography to trigger bone formation within a scaffold for the first time in the world. Collaboration with national research leaders on stem cell and animal testing of the new scaffolds will provide the ....Advanced micro-architecture and nanotopography for enhanced tissue growth in scaffolds. Tissue engineering scaffolds offer an urgently needed synthetic biomaterials solution to overcome disease transmission from donor transplants. This work will combine biomaterial chemistry and designed surface topography to trigger bone formation within a scaffold for the first time in the world. Collaboration with national research leaders on stem cell and animal testing of the new scaffolds will provide the necessary interdisciplinary approach to generate a new product for patients in need of bone regeneration. Australia will benefit from the contribution to medical science, the development of a new device for rapid prototyping tissue engineering scaffolds, retain biomaterials research expertise, and generate new biomedical products.Read moreRead less
Mesenchymal Progenitor Cells And Intervertebral Disc Repair
Funder
National Health and Medical Research Council
Funding Amount
$754,223.00
Summary
Low back pain affects 80% of the general population and is a major social and economic burden thus there is a clear need for effective treatment. Annual direct and indirect costs for low back pain exceeded $100 billion in the USA in 2006. We will use bone marrow derived multipotent progenitor cells in a regenerative strategy to undertake repair of the intervertebral disc in an ovine mechanical destabilisation model which reproduces early degenerative changes similar to those evident in man.
The Role Of Perlecan In Tensional Connective Tissues
Funder
National Health and Medical Research Council
Funding Amount
$605,037.00
Summary
Musculoskeletal diseases affect tension and weight bearing connective tissues which have notoriously poor repair capabilities. These conditions are difficult to treat clinically and surgical repair in many cases does not provide a return to optimal joint function impinging on the quality of life of afflicted individuals and their carers. Our project aims to better understand the structure and function of these tissues in health and disease with a view to improving repair strategies.
The Arthroplasty And Bariatric Surgery (ABS) Study: A Randomised Controlled Trial Of Laparoscopic Adjustable Gastric Banding Prior To Total Knee Arthroplasty
Funder
National Health and Medical Research Council
Funding Amount
$664,149.00
Summary
Knee replacement is a common surgical procedure in Australia (40,000 per year). More than 60% of this group are obese and this is associated with higher early (clinical) and long term (implant) survival complications. Laparoscopic adjustable gastric banding (LAGB) is an effective and safe means of achieving sustained weight loss. This study compares the outcomes of total knee replacement in groups of obese patients who have and have not undergone pre-knee replacement LAGB.
Biomechanics of the human spine measured using magnetic resonance imaging. Statistics show that 80% of the population suffer back pain at some time. However, because the spine is very complex our understanding of its mechanics and the causes of back pain are still limited. This project will investigate the anatomy and activity of the spinal muscles and the behaviour of the intervertebral disc in living subjects using innovative Magnetic Resonance Imaging techniques. Significant outcomes will be ....Biomechanics of the human spine measured using magnetic resonance imaging. Statistics show that 80% of the population suffer back pain at some time. However, because the spine is very complex our understanding of its mechanics and the causes of back pain are still limited. This project will investigate the anatomy and activity of the spinal muscles and the behaviour of the intervertebral disc in living subjects using innovative Magnetic Resonance Imaging techniques. Significant outcomes will be new definitive descriptions of the detailed anatomy of the spine and its mechanisms. This will enhance the accuracy and detail of models under development for predicting spinal function following disease, injury or surgical procedures.Read moreRead less