THE ROLE OF A NOVEL HYALURONIDASE IN THE TURNOVER OF CHONDROITIN SULPHATE GLYCOSAMINOGLYCANS IN CARTILAGE AND BONE
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
The degradation of complex carbohydrate structures occurs within specialised intracellular organelles (lysosomes). Their degradation occurs in a strictly defined sequence involving initial clipping into intermediate sized fragments which are each then degraded piece by piece from one end. In this proposal we seek to understand the role of a newly defined enzyme in the initial clipping process. This information will aid our understanding of skeletal pathology in a group of genetic disorders in wh ....The degradation of complex carbohydrate structures occurs within specialised intracellular organelles (lysosomes). Their degradation occurs in a strictly defined sequence involving initial clipping into intermediate sized fragments which are each then degraded piece by piece from one end. In this proposal we seek to understand the role of a newly defined enzyme in the initial clipping process. This information will aid our understanding of skeletal pathology in a group of genetic disorders in which complex carbohydrate degradation is impaired. In addition due to the widespread location of complex carbohydrates and their fundamental roles in tissue development and growth, the project has wider implications in diverse disease states such as cancer and wound repair.Read moreRead less
The Role Of Androgens In Osteoblast Development And Bone Metabolism.
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Maintenance of the skeleton involves the processes of bone formation by cells known as osteoblasts and bone breakdown by cells known as osteoclasts. When these processes become unbalanced, bone loss results, which is the basis of osteoporosis. The reduced bone mass found in osteoporosis leads to an increased susceptibility to bone fracture. 1 in 2 women and 1 in 3 men over the age of 60 will suffer a fracture due to osteoporosis. The increasing incidence of osteoporotic fractures has lead to ren ....Maintenance of the skeleton involves the processes of bone formation by cells known as osteoblasts and bone breakdown by cells known as osteoclasts. When these processes become unbalanced, bone loss results, which is the basis of osteoporosis. The reduced bone mass found in osteoporosis leads to an increased susceptibility to bone fracture. 1 in 2 women and 1 in 3 men over the age of 60 will suffer a fracture due to osteoporosis. The increasing incidence of osteoporotic fractures has lead to renewed efforts to understand the actions of hormones on bone. Androgens, the male sex hormones, have beneficial effects on skeletal growth and bone maintenance in both males and females by stimulating osteoblasts. It is believed that androgens act by binding to a specific protein known as the androgen receptor (AR), which is only found in androgen-responsive cells. Although it is well documented in human and animal models that androgens stimulate osteoblasts to increase the formation of bone, the way in which they act on osteoblasts remains poorly understood. The aim of this project is to investigate the effects of androgens at different stages of the developing osteoblast. This will be achieved by making transgenic mice in which the androgen receptor has been inactivated only in osteoblasts at specific stages of their development. We hypothesise that the inactivation of the androgen receptor will have dramatic effects on the development and function of osteoblasts. This project will help clarify the role androgens play in bone formation and will give fundamental insights into the basic biology of bone in both normal and disease processes. As androgens are one of the few agents that act to increase bone formation, understanding the way in which they act is important for the treatment of osteoporosis in males and females. We believe that this research is of great importance as osteoporosis becomes more prevalent in our aging population.Read moreRead less