Age-Related Changes In Body Composition And Fuel Metabolism: The Role Of Glucocorticoid Signalling In Osteoblasts
Funder
National Health and Medical Research Council
Funding Amount
$820,528.00
Summary
Our previous studies suggest that age related changes in fat tissue could be due to an increased level of glucocorticoids within bone forming cells (osteoblasts). Mice in which the level of glucocorticoids in osteoblasts is selectively decreased were no different from normal mice at a young age but with ageing were protected against development of obesity and diabetes. This project will examine how bone influences age related changes in fat mass and examine ways in which this might be prevented.
Treating and preventing painful fractures could be improved by strengthening cortical bone – the hard outer shell of all bones in the skeleton. We don’t know how cortical bone forms, but if we did, we could improve its strength. We have found that a brain-like network of cells inside the skeleton, called osteocytes, use a specific signal, called SOCS3, to make strong cortical bone. This study will find out how SOCS3 works and find new ways to make cortical bone strong and healthy.
Targeting Skeletal MTORC1 As A Novel Approach For The Treatment Of Diet-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$586,979.00
Summary
Diet-induced insulin resistance is a pathology that underlies type 2 diabetes. Elucidating the pathways and tissues that contribute to this condition is crucial for drug development. The skeleton has emerged as a critical insulin target tissue. We provide evidence that suppression of mTORC1, a complex over-activated by nutrients, in bone cells improves insulin sensitivity. In this study, we will determine if blocking mTORC1 function in bone cells can treat diet-induced insulin resistance.
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.
The Role Of Endogenous Glucocorticoids In The Pathogenesis Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$587,697.00
Summary
Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability. Recently, we found that the development of experimental OA in mice can be slowed if the effects of the body’s own (=endogenous) glucocorticoids were blocked locally. This project will determine how endogenous glucocorticoids accelerate the development of OA. We will further test whether treatment with drugs that block the actions of endogenous glucocorticoids can slow or prevent the development of OA.
Osteocytes, the most abundant and long-lived, yet least studied bone cell, are increasingly recognised as key controllers of bone remodelling and are implicated in many bone diseases. Our work is uncovering novel molecular and cellular pathways by which osteocytes act and survive in bone, which is generally an oxygen-deprived tissue. This will provide a rational basis to seek improved treatments of bone disease.
The Effect Of Titanium Surface Modification On The Immuno-regulation Of Osseointegration.
Funder
National Health and Medical Research Council
Funding Amount
$308,713.00
Summary
Titanium implants are an established treatment modality in both dentistry and orthopaedics. This project will determine how implant surface modification can modulate the inflammatory response and subsequent differentiation of stem cells involved in the process of integrating the implant with bone i.e. osseointegration. The identification of the molecular mechanisms involved will thus provide leads for novel ways to further to enhance the osseointegration process and improve clinical outcomes.