Identification Of Novel PTH Anabolic Targets In Osteoblasts
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
Osteoporosis is a major disease affecting Australians. Whilst there are a number of drugs available that will reduce bone loss, there are few drugs available that build new bone, and little is known of the action of these drugs. New targets have been identified that modulate bone formation, and this project aims to validate these in appropriate models and determine their mechanism of action.
Novel Strategies For The Treatment Of Bone Disease By Nutrient Activators Of Calcium-sensing Receptors
Funder
National Health and Medical Research Council
Funding Amount
$467,432.00
Summary
Osteoporosis is a major health problem in the Australian community and will worsen with an ageing population. This work aims to develop new strategies for the treatment of osteoporosis and associated fractures based on the nutritional and/or pharmacological activation of calcium-sensing receptors.
Determining The Influences Of Cell Stress And Heat Shock Factor-1 Action In Osteoclast Formation And Pathological Bone Loss.
Funder
National Health and Medical Research Council
Funding Amount
$657,287.00
Summary
Cancer and rheumatoid arthritis cause painful bone destruction. This occurs due to increased numbers of bone destroying cells called osteoclasts. We found stress responses in bone cells can increase osteoclast numbers by activating proteins inside the bone cells that encourage osteoclasts to form. We will thus study whether cell stress blocking drugs might stop bone loss. As arthritis and cancer both cause stress responses, this work could identify a new way that such diseases affect bone.
I am an orthopaedic surgeon and clinician-scientist based at Sydney’s largest children’s hospital. My goal is to improve treatments for children with traumatic injuries and bone deformity. I have worked in bone research for over 20 years. My current research interests are finding new treatments for drug-resistant bacterial infections, treating genetic bone disease, and developing new medical devices to help children’s bones grow straight.
Sclerostin: A Key Regulator Of Bone Mineralisation And Bone Catabolism
Funder
National Health and Medical Research Council
Funding Amount
$536,653.00
Summary
The regulation of bone mass is critical for many areas of human disease including osteoporosis, osteoarthritis, inflammatory bone loss conditions, e.g. rheumatoid arthritis, cancers of bone and problems relating to orthopaedic prosthesis failure. The osteocyte, the most abundant bone cell, plays a central role in normal bone biology and is likely key to these diseases. Sclerostin is one osteocyte product that may be a key to understanding how boneÍs mass and composition is controlled locally.
Delayed bone healing can be a considerable problem in both children and adults. Up to 10% of fractures fail to heal properly. An advanced understanding of the cellular responses in bone repair and their manipulation could improve the lives of many patients with orthopaedic problems. These studies will advance out knowledge of interventions to promote bone healing which could be translated rapidly into clinical care.
The osteocyte, the most abundant bone cell, likely plays a central role in bone biology and diseases, such as osteoporosis. The osteocyte product Sclerostin is a key regulator of bone mass. We are characterising novel pathways of sclerostin action via the expression of microRNAs.
The Role Of EphrinB1 Reverse Signalling In Osteogenic Differentiation During Skeletal Development And Osteoporosis
Funder
National Health and Medical Research Council
Funding Amount
$567,292.00
Summary
The present proposal will identify the importance of ephrinB1 during the deregulation of bone remodelling that occurs in osteoporosis, by deleting ephrinB1 in committed osteoblast precursor cells in a mouse model of osteoporosis. Knowledge gained from this proposal could potentially translate into alternative therapeutic treatment strategies for patients with osteoporosis with the use of Eph/ephrin targeted drugs currently being developed for cancer treatment.
The Role Of Sorting Nexin 27 In Cargo-trafficking During Skeletal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$623,327.00
Summary
Skeletal diseases encompass a devastating set of disorders ranging from heritable skeletal dysplasia’s such as dwarfism through to degenerate diseases like osteoporosis. This research project aims to determine the role of a protein called Sorting Nexin 27 (SNX27), normally involved in the transport of intracellular cargo (e.g. growth factor receptors), in the maintenance of the skeleton and its potential contribution to the pathogenesis of skeletal disorders.
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.