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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.
The Central Role Of The Osteocyte In Skeletal Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
Bone diseases affect more people than any other group, carry a huge and growing socioeconomic cost, yet their aetiologies are not fully determined. This study will elucidate the role of the resident bone cell, the osteocyte, in prevalent bone diseases such as osteoporosis, osteoarthritis and related orthopaedic conditions, rheumatoid arthritis, bone cancer, and in systemic metabolism. The goal is to provide the knowledge and mechanisms for developing improved treatments and patient outcomes.
Twist-1 Mediated Regulation Of Multipotential Mesenchymal Stem Cell Self-Renewal And Cell Fate Determination
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
In Australia, there is an increasing incidence of fractures and skeletal related problems that require surgical intervention and rehabilitation therapy. These are complex processes that involve the coordination of different bone and immune cells. We will investigate important regulatory molecules that mediate bone-cartilage stem cell recruitment and development during normal skeletal growth and remodelling. This study will help advance therapies for fracture repair and joint deterioration.
Histone Demethylase KDM6A Is A Novel Target For Treating Craniosynostosis In Children With Saethre-Chotzen Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$548,854.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fused coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting this key molecular regulator with chemical inhibitors will help prevent the premature fusion of cranial sutures.
Assessment Of The Properties Of Mesenchymal Stem Cells And Their Role In Skeletal Tissue Repair And Disease
Funder
National Health and Medical Research Council
Funding Amount
$751,854.00
Summary
There is currently a steady increase in surgical intervention and rehabilitation therapy for bone related fractures due to trauma or osteoporosis as a consequence of an aging population. Bone regeneration involves the coordinated participation of skeletal precursor cells, blood vessels and immune cells recruited from the surrounding tissues. This proposal examines the mechanisms mediating the maintenance and recruitment of skeletal precursor cells to sites of bone damage.
ROLE OF EPHRIN-EPH SIGNALLING IN THE FORMATION PHASE OF BONE REMODELLING
Funder
National Health and Medical Research Council
Funding Amount
$538,459.00
Summary
Bone is constantly being renewed through bone remodelling. An amount of bone is removed by osteoclasts, and bone-forming osteoblasts make just enough to fill the space. We discovered that proteins known as ephrins are produced by osteoblasts, and act on neighbouring osteoblasts to help them make new bone. We aim to define how ephrins increase bone formation in remodelling, how that is controlled and how it might be used to find ways to increase bone formation.
Determining The Genetic Basis Of Skeletal Dysplasias Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$110,068.00
Summary
Osteoporosis is a common condition in Australia, yet treatment options are still limited. Study of rare genetic bone conditions known collectively as skeletal dysplasias have already led to the development of two new osteoporosis drug treatments. My project aims to identify the causative gene for several skeletal dysplasias, and to determine how these genes are involved in the development and maintenance of bone. This knowledge may then translate into new osteoporosis therapies.
Mesenchymal Stem Cell Maintenance And Recruitment During Skeletal Repair Are Dependent On EphB-ephrinB Signalling
Funder
National Health and Medical Research Council
Funding Amount
$611,827.00
Summary
There is currently a steady increase in surgical intervention and rehabilitation therapy for bone related fractures due to trauma or osteoporosis as a consequence of an aging population. Bone regeneration involves the coordinated participation of skeletal precursor cells, blood vessels and immune cells recruited from the surrounding tissues. This proposal examines the mechanisms mediating the maintenance and recruitment of skeletal precursor cells to sites of bone damage.
Bone mass is regulated by a number of processes that originate in the brain, however, the mechanism whereby the bone signals to the brain is unknown. Osteoblasts, the cells that form bone, secrete a hormone, osteocalcin that signals in other tissues to control energy and glucose homeostasis. This proposal explores osteocalcin signalling in bone as well as in the brain as a potential feedback from bone to the brain.
Twist-1 Inhibits MSC Osteoblast Differentiation During Osteoporosis Via Direct Regulation Of The Wnt Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$482,704.00
Summary
There is a predicted dramatic increase in the number of orthopaedic related problems that require surgical intervention and rehabilitation therapy in the coming decade associated with higher incidences of bone diseases as a consequence of an aging population. This proposal seeks to determine whether the transcription factor, Twist-1 plays a central role in regulating the growth and differentiation of skeletal progenitors during bone loss following the onset of osteoporosis.