The Role of the Osteoblast in Mediating Glucocorticoid-Induced Metabolic Dysfunction

Summary

To investigate how glucocorticoid affect the regulation of glucose and lipid metabolism.

Supervisor(s)

Professor Markus Seibel, Associate Professor Hong Zhou

Research Location

Concord - ANZAC Research Institute

Program Type

Masters/PHD

Synopsis

Background:
Glucocorticoids are widely used and effective drugs but many patients suffer from serious adverse effects such as osteoporosis, obesity and diabetes. The mechanisms responsible for these effects are ill defined.
We have recently examined the effects of exogenous glucocorticoids on bone and energy metabolism using cutting-edge transgenic technology. To our great surprise and excitement, we found that transgenic mice, in which glucocorticoid signalling was disrupted in osteoblasts only, were not only pro¬tected from the bone-wasting effects of glucocorticoids but also from hyper¬lipidaemia and obesity. These results clearly indicate that the effects of exogenous glucocorticoids on fuel metabolism are to a significant part mediated through bone cells, specifically the osteoblast.
These novel findings support very recent concepts that bone cells may act as hormonal regulators of glucose metabolism, and may play an important role in the development of obesity. Also, our findings may aid the development of new strategies to treat or prevent unwanted glucocorticoids effects on energy metabolism. We now aim to establish the mechanisms that govern glucocorticoid action in osteoblasts and how these affect the regulation of glucose and lipid metabolism.

Project hypothesis:
The systemic metabolic effects of glucocorticoids are mediated by the osteoblast.

Project aims:
1. To define the effect of glucocorticoids on the crosstalk between osteoblasts and adipocytes in vitro and in vivo.
2. To define how glucocorticoids affect the synthesis, metabolism and signalling of osteoblast-derived products that act as mediators between bone and energy metabolism.

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Keywords

Glucocorticoids, Osteoporosis, Obesity, diabetes, Bone, Pharmacology & therapeutics

Opportunity ID

The opportunity ID for this research opportunity is: 1160

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