The Role of Endogenous Glucocorticoids in Autoimmune Arthritis

Summary

This is ongoing project to define the role and machinism of endogenous glucocorticoids in autoimmune arthritis.

Supervisor(s)

Associate Professor Hong Zhou, Professor Markus Seibel

Research Location

Concord - ANZAC Research Institute

Program Type

Masters/PHD

Synopsis

Background: Administered at pharmaco­logical doses, glucocorticoids are of great clinical benefit in the treat­ment of autoimmune disorders. While the effects of these exogenous glucocorticoids on inflammatory pro­cesses are well researched, the role of endogenous glucocorticoids in autoimmune arthritis remains unknown. Using cutting-edge transgenic technology, we have found that disruption of glucocorticoid signalling in bone forming cells (osteoblasts) severely blunts autoimmune arthritis in mice (recently published in Arthritis & Rheum, 2009). These unexpected and exciting findings indicate that osteoblasts are able to modulate the immune-mediated inflammatory response via a gluco­corticoid-dependent pathway. We now aim to unravel the mechanisms that underlie these effects.

Project hypothesis: Osteoblasts, under the control of endogen­ous glucocorticoids, play a key role in media­ting and maintaining joint inflammation in autoimmune arthritis.

Project aims:
1. To demonstrate that cytokines increase osteoblastic glucocorticoids levels in osteoblasts.
2. To define local osteoblast-derived signals with pro-inflammatory action.
3. To define the response of synovial cells and neutrophils to osteoblastic-derived signals

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Keywords

Glucocorticoids, arthritis, Bone, cartilage, osteoblast, cytokines, Cell biology, Pharmacology & therapeutics

Opportunity ID

The opportunity ID for this research opportunity is: 1159

Other opportunities with Associate Professor Hong Zhou

Other opportunities with Professor Markus Seibel