@article {17059,
	title = {Estrogen modulates estrogen receptor alpha and beta expression, osteogenic activity, and apoptosis in mesenchymal stem cells (MSCs) of osteoporotic mice},
	journal = {J Cell Biochem Suppl},
	volume = {Suppl 36},
	year = {2001},
	note = {Zhou, S Zilberman, Y Wassermann, K Bain, S D Sadovsky, Y Gazit, D eng Research Support, Non-U.S. Gov{\textquoteright}t 2001/07/17 10:00 J Cell Biochem Suppl. 2001;Suppl 36:144-55.},
	pages = {144-55},
	type = {Journal Article},
	abstract = {In the mouse, ovariectomy (OVX) leads to significant reductions in cancellous bone volume while estrogen (17beta-estradiol, E2) replacement not only prevents bone loss but can increase bone formation. As the E2-dependent increase in bone formation would require the proliferation and differentiation of osteoblast precursors, we hypothesized that E2 regulates mesenchymal stem cells (MSCs) activity in mouse bone marrow. We therefore investigated proliferation, differentiation, apoptosis, and estrogen receptor (ER) alpha and beta expression of primary culture MSCs isolated from OVX and sham-operated mice. MSCs, treated in vitro with 10(-7) M E2, displayed a significant increase in ERalpha mRNA and protein expression as well as alkaline phosphatase (ALP) activity and proliferation rate. In contrast, E2 treatment resulted in a decrease in ERbeta mRNA and protein expression as well as apoptosis in both OVX and sham mice. E2 up-regulated the mRNA expression of osteogenic genes for ALP, collagen I, TGF-beta1, BMP-2, and cbfa1 in MSCs. In a comparison of the relative mRNA expression and protein levels for two ER isoforms, ERalpha was the predominant form expressed in MSCs obtained from both OVX and sham-operated mice. Cumulatively, these results indicate that estrogen in vitro directly augments the proliferation and differentiation, ERalpha expression, osteogenic gene expression and, inhibits apoptosis and ERbeta expression in MSCs obtained from OVX and sham-operated mice. Co-expression of ERalpha, but not ERbeta, and osteogenic differentiation markers might indicate that ERalpha function as an activator and ERbeta function as a repressor in the osteogenic differentiation in MSCs. These results suggest that mouse MSCs are anabolic targets of estrogen action, via ERalpha activation. J. Cell. Biochem. Suppl. 36: 144-155, 2001.},
	keywords = {Alkaline Phosphatase/genetics/metabolism Animals *Apoptosis Bone Marrow Cells/metabolism/pathology Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins/genetics/metabolism Cell Differentiation Cell Division Cells, Cultured Collagen/genetics/metabolism *Collagen Type I Core Binding Factor Alpha 1 Subunit Estradiol/*pharmacology Estrogen Receptor alpha Estrogen Receptor beta Female Immunohistochemistry Mesoderm/pathology Mice *Neoplasm Proteins Osteogenesis/*drug ef, Estrogen/genetics/*metabolism Reverse Transcriptase Polymerase Chain Reaction Stem Cells/metabolism/*pathology Transcription Factors/genetics/metabolism Transforming Growth Factor beta/genetics/metabolism Transforming Growth Factor beta1, Messenger/metabolism Receptors},
	issn = {0733-1959 (Print) 0733-1959 (Linking)},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/11455579},
	author = {Zhou, S. and Zilberman, Y. and Wassermann, K. and Bain, S. D. and Sadovsky, Y. and Gazit, D.}
}
