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..
Analysis Of The Osteoclast Methylome For Characterisation Of Epigenetic Mechanisms Underlying Metabolic Bone Disease
Funder
National Health and Medical Research Council
Funding Amount
$299,018.00
Summary
A large number of genetic variants have been identified that have a role in osteoporosis, however for many of these, the mechanism by which they influence the disease remains to be determined. This study will fill a critical knowledge gap by investigating the epigenetic control of gene expression in osteoclasts (bone resorbing cells). This research will generate a unique international resource that will provide foundation data to understand and treat this prevalent and debilitating bone disease.
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.
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