Since the introduction of glucocorticoids (GCs) in the treatment of rheumatoid arthritis in 1949, GC therapy has been associated with a number of adverse effects. Long-term use of GCs can result in growth retardation during childhood due to their actions on growth plate chondrocytes, although the exact mechanisms involved are unclear. The work of this thesis has investigated the cellular and molecular mechanisms involved in mediating GC effects at the growth plate. Affymetrix microarray has been used to identify and characterise the expression of lipocalin 2, a novel GC-responsive chondrocyte gene which may contribute to GC-induced growth retardation in the growth plate. In vitro and in vivo studies have also been used to examine the role of the cell cycle regulator, p21WAF1/CIP1 in GC-induced growth retardation. Finally, the growth plate sparing effects of a novel GC receptor modulator, AL-438, have also been identified. AL438, has reduced effects on bone growth compared to Dex, but maintains similar anti-inflammatory efficacy. This work has not only determined novel mechanisms of GC-induced growth retardation, but has also advanced the search for novel GC receptor modulators with reduced adverse effects.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:495186 |
| Date | January 2008 |
| Creators | Owen, Helen C. |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/162/ |
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