title: Induction of estrogen receptor alpha expression with decoy oligonucleotide targeted to NFATc1 binding sites in osteoblasts.
abstract: The nuclear factor of activated T cell cytoplasmic 1 (NFATc1) is a member of the NFAT family and is strictly implicated in the growth and development of bone. Most studies have focused on the effects of NFATc1 activation on osteoclastogenesis. On the contrary, the specific roles of NFAT in osteoblast differentiation are not well understood and, in some instances, reports of its role are contradictory. In the present study, we demonstrated that NFATc1 was involved in the transcriptional regulation of human estrogen receptor alpha (ERalpha) gene in SaOS-2 osteoblastic like cells. NFATc1 was specifically recruited "in vivo" at C and F distal promoters of ERalpha gene. In addition, it is here identified as the negative transcription factor removed by the RA4-3'decoy oligonucleotide able to induce ERalpha expression in osteoblasts. Ca(2+)/calcineurin-NFAT-mediated signaling pathways and ERalpha-dependent signals are involved in diverse cellular reactions by regulating gene expression under both physiological and pathological conditions. Therefore, our data might be useful for proper manipulation of NFATc1- and ERalpha-mediated cellular reactions in different bone disorders, such as osteoporosis.
authors: Department of Biochemistry and Molecular Biology, Molecular Biology Section, Ferrara, Italy.
authors: Letizia
authors: L
authors: Penolazzi
authors: Margherita
authors: M
authors: Zennaro
authors: Elisabetta
authors: E
authors: Lambertini
authors: Elisa
authors: E
authors: Tavanti
authors: Elena
authors: E
authors: Torreggiani
authors: Roberto
authors: R
authors: Gambari
authors: Roberta
authors: R
authors: Piva
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D050778:NFATC Transcription Factors / Q000502:physiology*; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014162:Transfection
chemical_list: D047628:Estrogen Receptor alpha; D050778:NFATC Transcription Factors; D009841:Oligonucleotides