There are a number of important medical conditions that are characterised by a loss of bone. These include osteoporosis, cancer-induced bone loss, and the bone loss that causes loosening of orthopaedic prostheses. Bone loss is understood to be due to an excess of bone resorption by osteoclasts in relation to bone formation. Understanding of the regulation of osteoclast formation and activity has increased greatly in the last few years, but important questions remain. In particular, more informat ....There are a number of important medical conditions that are characterised by a loss of bone. These include osteoporosis, cancer-induced bone loss, and the bone loss that causes loosening of orthopaedic prostheses. Bone loss is understood to be due to an excess of bone resorption by osteoclasts in relation to bone formation. Understanding of the regulation of osteoclast formation and activity has increased greatly in the last few years, but important questions remain. In particular, more information is needed about the process of human osteoclast formation. We have devised a novel cell culture model of human osteoclast formation, in which osteoclast precursor cells mature into osteoclasts under the influence of human osteoblast cells. The importance of this model is that it allows us, for the first time, to investigate the role, and the potential relevance in human disease, of agents that positively and negatively affect osteoclasts. We intend also to use this model to study the way in which cancer cells in bone cause bone loss, as well as the involvement of cells of the immune system in osteoclast formation, in normal bone and in inflammatory conditions.Read moreRead less
Snail Family Proteins Regulate Stem Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$288,650.00
Summary
This research aims to discover the role of a family of genes in regulating stem cells. These genes are known to turn other genes off and we have shown that this family is required to maintain stem cells in animal tissues. The current research seeks to determine which genes are normally switched off in order to maintain normal stem cells. We also aim to determine if turning these genes on leads to cancer formation.
Role Of Beta-catenin And Its Regulator FAM In Haemopoietic Stem Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$506,500.00
Summary
Haemopoietic stem cells (HSC) are currently the best characterised adult stem cell (SC) population and currently the only SC population used in cellular therapy. Adult HSC reside in the bone marrow and it is generally accepted that these rare cells cycle slowly and maintain themselves by a process involving self renewal. The cellular physiology that underlies HSC self renewal is still to be defined and no single factor has been described which is able to induce substantial proliferation and expa ....Haemopoietic stem cells (HSC) are currently the best characterised adult stem cell (SC) population and currently the only SC population used in cellular therapy. Adult HSC reside in the bone marrow and it is generally accepted that these rare cells cycle slowly and maintain themselves by a process involving self renewal. The cellular physiology that underlies HSC self renewal is still to be defined and no single factor has been described which is able to induce substantial proliferation and expansion of HSC in a defined system while maintaining critical stem cell properties. Like other SC, a critical characteristic of the rare HSC population of cells is their ability to maintain their unique stem cell properties in vivo (the process of self-renewal) while generating more committed cells which will form large numbers of differentiated and specialized mature blood cells. Recent evidence that HSC can repair other organs under some circumstances raises the possibility that this adult SC population could provide an alternative to embryonic stem cells for many stem cell therapies. If this is the case the therapeutic application of HSC becomes significantly broader. Critical to development of such applications will be an understanding of HSC self renewal and development and new approaches to expand this limited cell population. Major progress in this area will require the definition of both the intrinsic and extrinsic mechanisms that control HSC maintenance and self-renewal. Any findings in this area will have major clinical significance and be of enormous benefit to the community. Here we focus on the role of a known intrinsic regulator of SC behaviour (beta-catenin) with the aim of establishing its role in the maintenance of HSC and its regulation by a novel cofactor (FAM). We will determine if the level of beta-catenin is critical in the maintenance and-or differentiation of haemopoietic stem cells and what role FAM plays in this regulation.Read moreRead less