Penolazzi Letizia, Zennaro Margherita, Lambertini Elisabetta, Tavanti Elisa, Torreggiani Elena, Gambari Roberto, Piva Roberta
Department of Biochemistry and Molecular Biology, Molecular Biology Section, Ferrara, Italy.
Mol Pharmacol. 2007 Jun;71(6):1457-62. doi: 10.1124/mol.107.034561. Epub 2007 Mar 27.
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.
活化T细胞核因子胞质1（NFATc1）是NFAT家族的成员，与骨骼的生长发育密切相关。大多数研究集中于NFATc1激活对破骨细胞生成的影响。相反，NFAT在成骨细胞分化中的具体作用尚未完全明确，在某些情况下，关于其作用的报道相互矛盾。在本研究中，我们证明NFATc1参与了人雌激素受体α（ERα）基因在SaOS-2成骨样细胞中的转录调控。NFATc1在体内特异性地募集到ERα基因的C和F远端启动子处。此外，它被鉴定为能被RA4-3'诱饵寡核苷酸去除的负性转录因子，该诱饵寡核苷酸能够诱导成骨细胞中ERα的表达。Ca(2+)/钙调磷酸酶-NFAT介导的信号通路和ERα依赖性信号通过在生理和病理条件下调节基因表达参与多种细胞反应。因此，我们的数据可能有助于在不同的骨疾病（如骨质疏松症）中正确调控NFATc1和ERα介导的细胞反应。
