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The cellular and molecular mechanisms of glucocorticoid-induced growth retardation

Owen, Helen C (2008) The cellular and molecular mechanisms of glucocorticoid-induced growth retardation. PhD thesis, University of Glasgow.

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Abstract

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.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Glucocorticoids, Bone, Growth Plate, Chondrocytes, AL-438, Lipocalin 2, p21, Microarray, Growth Retardation
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Farquharson, Dr Colin and Ahmed, Dr Syed Faisal
Date of Award: February 2008
Depositing User: Dr Helen. C Owen
Unique ID: glathesis:2008-02-162
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 22 Aug 2008
Last Modified: 10 Dec 2012 13:16
URI: http://theses.gla.ac.uk/id/eprint/162

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