Reference - Detail
| RRC ID | 43320 |
|---|---|
| Author | Owen HC, Roberts SJ, Ahmed SF, Farquharson C. |
| Title | Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. |
| Journal | Am J Physiol Endocrinol Metab |
| 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. |
| Volume | 294(6) |
| Pages | E1023-34 |
| Published | 2008-6-1 |
| DOI | 10.1152/ajpendo.00586.2007 |
| PII | 00586.2007 |
| PMID | 18381927 |
| MeSH | Acute-Phase Proteins / biosynthesis* Acute-Phase Proteins / genetics Animals Anti-Inflammatory Agents / pharmacology* Cell Differentiation / drug effects Cell Line Cell Proliferation / drug effects Chondrocytes / cytology Chondrocytes / drug effects* Chondrocytes / metabolism Chondrocytes / physiology Crosses, Genetic Dexamethasone / pharmacology* Gene Expression / drug effects Gene Expression Profiling Growth Plate / drug effects Growth Plate / physiology Histocytochemistry Lipocalin-2 Lipocalins / biosynthesis* Lipocalins / genetics Mice Mice, Inbred C57BL Mice, Inbred CBA Oligonucleotide Array Sequence Analysis Oncogene Proteins / biosynthesis* Oncogene Proteins / genetics RNA, Messenger / biosynthesis RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction |
| IF | 3.469 |
| Times Cited | 50 |
| WOS Category | PHYSIOLOGY ENDOCRINOLOGY & METABOLISM |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | ATDC5(RCB0565) |