Cellular Responses To Thrombin In Skeletal Pathology
Funder
National Health and Medical Research Council
Funding Amount
$120,775.00
Summary
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. The enzyme thrombin is involved in blood coagulation but also causes bone cells to alter their behaviour. Thrombin stimulates proliferation of bone-forming cells and protects them from premature death. Thrombin also stimulates t ....Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. The enzyme thrombin is involved in blood coagulation but also causes bone cells to alter their behaviour. Thrombin stimulates proliferation of bone-forming cells and protects them from premature death. Thrombin also stimulates the breakdown of bone. We will investigate how thrombin's effects on bone cell behaviour influence the course of bone healing. We will also determine how thrombin stimulates bone breakdown and increases survival of bone-forming cells. This study will contribute to the understanding of how bone cells function in health and disease.Read moreRead less
Evaluation Of The Therapeutic Potential Of SFTI-FCQR, A Novel Kallikrein 4-specific Protease Inhibitor
Funder
National Health and Medical Research Council
Funding Amount
$167,303.00
Summary
Prostate and ovarian cancers are on the rise in Australia's ageing population. In previous work, we have studied prostate and ovarian cancer cells that we have engineered to make the protease KLK4. These cells show signs associated with aggressive tumours and in particular may have some of the changes found in cancer cells that spread from their site of origin (metastasize). In this project, we will look at a drug-like molecule that we have designed with the aim of blocking the activity of KLK4.
The Role Of Protease-activated Receptor-2 In Regulation Of Bone Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$216,100.00
Summary
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. We have recently demonstrated the presence of a receptor called PAR-2 on bone-forming cells. We have also shown that activation of PAR-2 inhibits the development of bone-resorbing cells (osteoclasts) in response to hormones. We ....Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. We have recently demonstrated the presence of a receptor called PAR-2 on bone-forming cells. We have also shown that activation of PAR-2 inhibits the development of bone-resorbing cells (osteoclasts) in response to hormones. We plan to investigate the mechanism of this effect, as well as to identify how PAR-2 activation modulates other responses of bone cells to hormones. Molecules that activate PAR-2 are present in bone in certain disease situations, but it is not known what activates PAR-2 in bone under normal conditions. We will identify physiological activators of PAR-2 within bone.Read moreRead less