Furin: Carving-up Vital Substrates For Bone Remodelling And Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$815,972.00
Summary
Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures. It is caused by an imbalance between the cells that are constantly reabsorbing and reforming bone. The proposed project will address furin as a novel regulator of bone remodelling.
Short-term Use Of Intermittent PTH To Accelerate Healing Of Stress Fractures And During Bisphosphonate Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$633,331.00
Summary
Osteoporosis treatments prevent fractures by hindering cells that erode the skeleton. Normally, those cells also repair injuries like stress fractures. Some patients, treated for long periods, can suffer fractures because the treatment slows bone healing. We have an innovative model to test alternative treatments to accelerate stress fracture healing, while osteoporosis treatment continues. This could prevent unusual stress fractures, in patients who still need the bone-sparing effectiveness of ....Osteoporosis treatments prevent fractures by hindering cells that erode the skeleton. Normally, those cells also repair injuries like stress fractures. Some patients, treated for long periods, can suffer fractures because the treatment slows bone healing. We have an innovative model to test alternative treatments to accelerate stress fracture healing, while osteoporosis treatment continues. This could prevent unusual stress fractures, in patients who still need the bone-sparing effectiveness of osteoporosis treatment.Read moreRead less
Novel Pathways Involving APC And PAR-2 In Cartilage Degradation In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$448,834.00
Summary
Loss of the cartilage that normally lines the ends of bones is central to joint failure in arthritis and the need for replacement surgery. There are presently no treatments that stop cartilage breakdown in joint disease. This project investigates the role of a new pathway not previously thought to be active in cartilage, in the progressive damage seen in arthritis. Successful completion of these studies may provide a novel new strategy to treat joint disease.
Influence Of Osteocytes On Anabolic Bone Therapies
Funder
National Health and Medical Research Council
Funding Amount
$586,965.00
Summary
This project seeks to define the influence of changes in gene expression in cells called osteocytes, that exist within the substance of bone. These cells form a communication network within the bones of the skeleton, and appear to influence bone formation; changes in gene expression by these cells could influence the efficacy of current and emerging osteoporosis therapies.
INVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC CELL MATRIX METALLOPROTEINASES
Funder
National Health and Medical Research Council
Funding Amount
$331,320.00
Summary
Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem w ....Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem will increase in severity over the next few decades. American Bureau of Census data indicate that between 1990 to 2010 the number of people >45 years will increase from 82 to 124 million, the number of elderly in emerging countries will also increase between 200 to 400% in the next 30 years. In the United States, back-pain is the second most common reason that people visit a physician and medical conditions related to back-pain account for more hospitalisations than any other musculoskeletal disorder. Despite its high incidence, associated problems of incapacity and economic implications, costed at $100 million per annum in Australia in 1992, and US$100 billion globally in 1999-2000 (Dorland Data Networks, PA, USA) the causes of low back-pain are still poorly understood. Disc disease is responsible for 23-40% of all cases of low back-pain. The management of discogenic low back-pain is currently empirical, directed either toward life-style changes to minimise symptomatology or to surgical resection or spinal arthrodesis to restrict articulation. Based on our recent findings and those of colleagues over the last 16 years, it is our strong conviction that it should be possible with a better understanding of disease mechanisms and with the use of modern technologies to inhibit, reverse or ideally prevent disc degeneration. Without such basic research there will be no scientific foundation upon which prospective therapies may be based.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
Tendon injury is one of the most common health problems worldwide and affects almost everyone at some point in particular the aging populaiton. However, the current treatments are not well defined. We identifed an extracellular molecules SPARC that potentially plays an important role in tendon function. The aim of this study is to examine the role of SPARC in tendon development, homestasis and degenerative using transgenic mice and gene therapy. We predict that SPARC will have therapeutic value ....Tendon injury is one of the most common health problems worldwide and affects almost everyone at some point in particular the aging populaiton. However, the current treatments are not well defined. We identifed an extracellular molecules SPARC that potentially plays an important role in tendon function. The aim of this study is to examine the role of SPARC in tendon development, homestasis and degenerative using transgenic mice and gene therapy. We predict that SPARC will have therapeutic value for the treatment of tendinopathy.Read moreRead less
The Role Of TNF Family Members TWEAK And TNF-alpha In Bone Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$566,946.00
Summary
Bone remodelling, or turnover, is the process by which bone is broken down by osteoclasts and replaced by osteoblasts. Disruption of this process is the cause of many bone-related diseases that affect millions of Australians and countless others worldwide. It is controlled by the complex interactions of a large number of systemic factors (hormones) and locally acting agents, such as chemokines and cytokines, the details of which are not fully understood. Each of these factors, however, is a pote ....Bone remodelling, or turnover, is the process by which bone is broken down by osteoclasts and replaced by osteoblasts. Disruption of this process is the cause of many bone-related diseases that affect millions of Australians and countless others worldwide. It is controlled by the complex interactions of a large number of systemic factors (hormones) and locally acting agents, such as chemokines and cytokines, the details of which are not fully understood. Each of these factors, however, is a potential therapeutic target. Pro-inflammatory cytokines, those that are associated with inflammatory diseases such as Rheumatoid Arthritis (RA), are known to have key roles in both the physiology and pathology of bone. TWEAK is a recently described member of the TNF family of cytokines. We have shown that TWEAK is a novel mediator of inflammatory arthritis in mouse model systems and is therefore a likely candidate as a therapeutic target. We now have extensive preliminary data to suggest that TWEAK is involved in human RA, and also in the regulation of normal bone remodelling. TWEAK therefore may be implicated in a wide spread of bone diseases, including osteoporosis. We believe it is of great importance to perform a thorough analysis of TWEAK in bone biology, and we propose to do so.Read moreRead less
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