Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes
Article
Owen, H., Roberts, S., Ahmed, S. and Farquharson, C. 2008. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. American Journal of Physiology - Endocrinology and Metabolism. 294 (6), pp. E1023-E1034. https://doi.org/10.1152/ajpendo.00586.2007
Type | Article |
---|---|
Title | Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes |
Authors | Owen, H., Roberts, S., Ahmed, S. and Farquharson, C. |
Abstract | Glucocorticoids (GC) are commonly used anti-inflammatory drugs, but long-term use can result in marked growth retardation in children due to their actions on growth plate chondrocytes. To gain an insight into the mechanisms involved in GC-induced growth retardation, we performed Affymetrix microarray analysis of the murine chondrogenic cell line ATDC5, incubated with 10(-6) M dexamethasone (Dex) for 24 h. Downregulated genes included secreted frizzled-related protein and IGF-I, and upregulated genes included serum/GC-regulated kinase, connective-tissue growth factor, and lipocalin 2. Lipocalin 2 expression increased 40-fold after 24-h Dex treatment. Expression increased further after 48-h (75-fold) and 96-h (84-fold) Dex treatment, and this response was Dex concentration dependent. Lipocalin 2 was immunolocalized to both proliferating and hypertrophic growth plate zones, and its expression was increased by Dex in primary chondrocytes at 6 h (3-fold, P < 0.05). The lipocalin 2 response was blocked by the GC-receptor antagonist RU-486 and was increased further by the protein synthesis blocker cycloheximide. Proliferation in lipocalin 2-overexpressing cells was less than in control cells (49%, P < 0.05), and overexpression caused an increase in collagen type X expression (4-fold, P < 0.05). The effects of lipocalin 2 overexpression on chondrocyte proliferation (64%, P < 0.05) and collagen type X expression (8-fold, P < 0.05) were further exacerbated with the addition of 10(-6) M Dex. This synergistic effect may be explained by a further increase in lipocalin 2 expression with Dex treatment of transfected cells (45%, P < 0.05). These results suggest that lipocalin 2 may mediate Dex effects on chondrocytes and provides a potential novel mechanism for GC-induced growth retardation. |
Keywords | microarray; growth retardation |
Publisher | American Physiological Society |
Journal | American Journal of Physiology - Endocrinology and Metabolism |
ISSN | 0193-1849 |
Electronic | 1522-1555 |
Publication dates | |
01 Jun 2008 | |
Online | 04 Jun 2008 |
Publication process dates | |
Deposited | 20 Apr 2016 |
Accepted | 28 Mar 2008 |
Output status | Published |
Digital Object Identifier (DOI) | https://doi.org/10.1152/ajpendo.00586.2007 |
Web of Science identifier | WOS:000256469200003 |
Language | English |
https://repository.mdx.ac.uk/item/86318
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