Opposing effects of glucocorticoids and Wnt signaling on Krox20 and mineral deposition in osteoblast cultures
| Autor: | Tommy Noh, Jon Cogan, Baruch Frenkel, Elisheva Smith, Dilan B. Samarawickrama, Nathalie Leclerc |
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| Rok vydání: | 2008 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Cellular differentiation Biology Biochemistry Cell Line Wnt3 Protein Mice Calcification Physiologic Heat Shock Transcription Factors Wnt3A Protein Internal medicine medicine Animals Glucocorticoids Molecular Biology Transcription factor Early Growth Response Protein 2 Osteoblasts Wnt signaling pathway Cell Differentiation Osteoblast Cell Biology DNA-Binding Proteins Wnt Proteins RUNX2 medicine.anatomical_structure Endocrinology Gene Expression Regulation DKK1 Osteocalcin biology.protein Signal Transduction Transcription Factors |
| Zdroj: | Journal of Cellular Biochemistry. 103:1938-1951 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.21587 |
| Popis: | Krox20 is expressed in osteoblasts and chondrocytes, and is required for trabecular bone formation during embryogenesis. Here we show by RT-qPCR and Western blot analysis that Krox20 is up-regulated during late stages of osteoblast differentiation in culture. Glucocorticoids (GCs) rapidly inhibit the expression of Krox20 as well its co-activator, HCF-1, resulting in inhibition of the Osteocalcin Krox20-binding Enhancer (OKE). GCs also inhibit expression of EGR1, EGR3, and EGR4. OKE activity, which is dependent on the presence of Runx2, was independent of the osteocalcin promoter Runx2 binding site. In contrast to GCs, activation of the Wnt, but not the BMP or the PTH signaling pathways, stimulated Krox20 expression as well as activity of the OKE. GC-mediated suppression of Krox20 expression was compromised, albeit not completely, in the presence of DKK1, suggesting that the inhibition occurs in both Wnt-dependent and Wnt-independent manners. Furthermore, Wnt3A partially rescued Krox20 expression in GC-arrested osteoblast cultures and this was accompanied by rescue of mineralization. These findings are consistent with a role for Krox20 in osteoblast function and suggest that this transcription factor may contribute to the opposing effects of GCs and Wnt signaling on bone formation. |
| Databáze: | OpenAIRE |
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