Osteoblastic differentiation induced by transcription factor decoy against estrogen receptor alpha gene

Biochemical and Biophysical Research Communications
E LambertiniR Piva

Abstract

Osteoblasts have been shown to express both isoforms of estrogen receptor (ER alpha and ER beta). As a tool for the study of endogenous regulation of these genes the decoy strategy was employed. Human MG-63 osteoblast-like cells were transfected with a DNA decoy molecule containing a putative negative cis-element (DNA-102) located in the C distal promoter of ER alpha gene. Using real-time quantitative RT-PCR, we found that the DNA-102, but not scrambled DNA, produced a 36-fold increase in the level of total ER alpha mRNA and a 12-fold increase in the level of mRNA for the F isoform that is transcribed from the upstream F promoter, which is predominantly used in osteoblasts. This effect appears to be controlled by estrogen since 17-beta-estradiol downregulated the mRNA increase. Notably, the same decoy was able to induce a 6-fold increase in ER beta mRNA transcription, indicating the coregulation of the ER alpha and ER beta expression. An increase in OPN but not in BMP4 expression was also observed. In addition, in decoy-treated cells, the cell growth decreased together with an increase in alkaline phosphatase activity. These findings indicated that DNA-102 decoy was able to induce a more differentiated osteoblastic phenotype. T...Continue Reading

Citations

Jun 14, 2005·Expert Opinion on Therapeutic Targets·Marek GniazdowskiMalgorzata Czyz
Sep 6, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Laetitia Lam Shang LeenAlain-Pierre Gadeau
Mar 26, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Delia B OngJonathan H Tobias
Jul 30, 2010·Journal of Clinical Periodontology·Qian Lu, Lijian Jin
Jan 18, 2006·In Vitro Cellular & Developmental Biology. Animal·W R HarmstonN Chandar
Mar 6, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gianluca AguiariLaura Del Senno

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