Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased susceptibility to fractures. Understanding the nature of bone loss may lead to the discovery of a new drug target for the treatment of osteoporosis..
The Role Of 'Orphan' Transporters In Bone Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$675,668.00
Summary
Osteoclasts (OCs) are giant multinucleated cells exclusively responsible for physiological bone degradation (resorption). Excessive OC activity leads to localised bone destruction (osteolysis) as observed in patients with osteoarthritis and underlies decreased bone mass and fragility fractures that are a hallmark of osteoporosis. This project examines the role of an orphan solute carrier transporter in OC function and its potential involvement in bone disease.
Regulation Of Bone Formation And Resorption By Osteoblastic EphrinB2/EphB4 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$648,479.00
Summary
Skeletal strength is maintained by balanced cycles of bone resorption and bone formation. Cells that live inside the bone matrix, osteocytes, are thought to co-ordinate this. We have found that two proteins, EphrinB2 and EphB4, exist on the surface of osteocytes and regulate bone formation and resorption. This project investigates how they do this, and whether interfering with or enhancing their signals could be used to increase bone strength in osteoporosis.
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.
Molecular Characterization Of V-ATPase V0 Domain Subunits E1 And E2 In Osteoclast
Funder
National Health and Medical Research Council
Funding Amount
$558,909.00
Summary
Osteoporotic fractures in the elderly are often linked to increased mortality rates. Excess bone resorption is a major contributor to the onset of the disease. The proposed project focuses on the investigation of the molecular mechanisms of acid secretion that is required for the bone degradation in body. The project will examine the role of the proton pump in bone resorption and seek potential targets for the treatment of osteoporosis.
gp130 is a protein expressed in all cells in the body; this project will analyse the influence of gp130 within the cells that form bone, the cells that destroy bone, and the cells that form a communication network within the bone matrix. Understanding the way this protein works will help us to understand how current therapies for osteoporosis work, and will help us to design new therapies.
IL-6 Classic And Trans-signalling In Bone Physiology And Pathology
Funder
National Health and Medical Research Council
Funding Amount
$731,372.00
Summary
This project seeks to determine whether it is possible to prevent bone loss associated with osteoporosis and inflammatory bowel disease by blocking interleukin 6. Two different methods of blockade will be tested, with the hope that one of these methods will have less side effects.
Structural And Functional Analyses Of Rat Receptor Activator Of NF-kb Ligand
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
Rat RANKL (Xu and Zheng, rat RANKL, AustraliaProvisional Patent PQ3147) has a variety of biological activities including osteoclast differentiation and polarization, and dendritic cell function. Overproduction or increased activity of RANKL can result in excessive osteoclast formation, activation, and bone resorption. This process contributes to many common bone lytic disorders such as osteoporosis, Paget's disease, bone metastatic diseases, arthritis, aseptic bone loosening and non-union of fra ....Rat RANKL (Xu and Zheng, rat RANKL, AustraliaProvisional Patent PQ3147) has a variety of biological activities including osteoclast differentiation and polarization, and dendritic cell function. Overproduction or increased activity of RANKL can result in excessive osteoclast formation, activation, and bone resorption. This process contributes to many common bone lytic disorders such as osteoporosis, Paget's disease, bone metastatic diseases, arthritis, aseptic bone loosening and non-union of fractures. This proposal addresses the important and fundamental issue of RANKL regarding the role of molecular structure on its biological function. We have established that the TNF-like core domain is the functional domain, important for osteoclastogenesis, osteoclast polarisation and protecting against Fas-triggered apoptosis. This proposal will further characterise the mutant forms of the TNF-like core domain of RANKL using site directed mutagenesis and protein truncation analysis, and assess their respective binding activities to OPG and RANK, and their biological activities both in vitro and in vivo. It will lead us into better understanding of the structure-function relationship of RANKL. Ideally, we would like to develop a relative agent for the suppression of osteolysis in orthopaedic related diseases including osteoporosis. Such an optimized molecule could become a potent therapeutic agent that selectively inhibits osteoclast formation and bone resorption.Read moreRead less
Osteoporosis is a pathological loss of bone that affects many Australians. It occurs because of an excessive release of calcium from bone that is caused by the overactivity of the cells that break down bone, osteoclasts. We have studied two genes that are involved in the way these cells work and by a close examination of the the way they are regulated we hope to understand how osteoclasts are derived and how their activity is controlled. In particular we will look at two newly dicovered osteocla ....Osteoporosis is a pathological loss of bone that affects many Australians. It occurs because of an excessive release of calcium from bone that is caused by the overactivity of the cells that break down bone, osteoclasts. We have studied two genes that are involved in the way these cells work and by a close examination of the the way they are regulated we hope to understand how osteoclasts are derived and how their activity is controlled. In particular we will look at two newly dicovered osteoclast regulators called PPAR-gamma and PPAR-delta. These offer the opportunity for the development in the future of new, alternative drugs for the treatment of osteoporosis.Read moreRead less
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.