Abstract |
The efficacy of glucocorticoids (GCs) in treating a wide range of autoimmune and inflammatory conditions is blemished by severe side effects, including osteoporosis. The chief mechanism leading to GC-induced osteoporosis is inhibition of bone formation, but the role of RUNX2, a master regulator of osteoblast differentiation and bone formation, has not been well studied. We assessed effects of the synthetic GC dexamethasone (dex) on transcription of RUNX2-stimulated genes during the differentiation of mesenchymal pluripotent cells into osteoblasts. Dex inhibited a RUNX2 reporter gene and attenuated locus-dependently RUNX2-driven expression of several endogenous target genes. The anti-RUNX2 activity of dex was not attributable to decreased RUNX2 expression, but rather to physical interaction between RUNX2 and the GC receptor (GR), demonstrated by co-immunoprecipitation assays and co-immunofluorescence imaging. Investigation of the RUNX2/GR interaction may lead to the development of bone-sparing GC treatment modalities for the management of autoimmune and inflammatory diseases.
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Authors | Theodora Koromila, Sanjeev K Baniwal, Yae S Song, Anthony Martin, Jian Xiong, Baruch Frenkel |
Journal | Journal of cellular biochemistry
(J Cell Biochem)
Vol. 115
Issue 1
Pg. 27-33
(Jan 2014)
ISSN: 1097-4644 [Electronic] United States |
PMID | 23943595
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 Wiley Periodicals, Inc. |
Chemical References |
- Core Binding Factor Alpha 1 Subunit
- Glucocorticoids
- Receptors, Glucocorticoid
- Runx2 protein, mouse
- Dexamethasone
- Alkaline Phosphatase
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Topics |
- Alkaline Phosphatase
(antagonists & inhibitors, metabolism)
- Animals
- Cell Differentiation
(drug effects)
- Cell Nucleus
(metabolism)
- Cells, Cultured
- Core Binding Factor Alpha 1 Subunit
(genetics, metabolism)
- Dexamethasone
(pharmacology)
- Glucocorticoids
(pharmacology)
- Mesenchymal Stem Cells
(cytology, drug effects)
- Mice
- Osteoblasts
(cytology, drug effects, metabolism)
- Pluripotent Stem Cells
(cytology, drug effects)
- Receptors, Glucocorticoid
(metabolism)
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