The Role of Endogenous Glucocorticoids in Autoimmune Arthritis
This is ongoing project to define the role and machinism of endogenous glucocorticoids in autoimmune arthritis.
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.
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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The opportunity ID for this research opportunity is: 1159
Other opportunities with Associate Professor Hong Zhou
- Glucocorticoid effects on bone: The role of the osteoblast
- The Role of the Osteoblast in Mediating Glucocorticoid-Induced Metabolic Dysfunction
Other opportunities with Professor Markus Seibel