Glucocorticoids antagonize RUNX2 during osteoblast differentiation in cultures of ST2 pluripotent mesenchymal cells.

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.

• 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)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

• Core Binding Factor Alpha 1 Subunit
• Glucocorticoids
• Receptors, Glucocorticoid
• Runx2 protein, mouse
• Dexamethasone
• Alkaline Phosphatase

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)