Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Centre national de la recherche scientifique UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.
PLoS One. 2013;8(1):e54837. doi: 10.1371/journal.pone.0054837. Epub 2013 Jan 24.
ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.
ERRα 是核受体家族的一个孤儿成员，其完全失活会导致雌性小鼠对衰老和雌激素耗竭引起的骨丢失产生抗性，与体内骨形成增加相关。此外，ERRα 还会负调控间充质细胞向成骨细胞谱系的体外分化以及成骨细胞成熟的后期步骤。我们试图确定 ERRα 对成骨细胞成熟的活性是否负责体内诱导的两种骨丢失中的一种或两种。为此，我们生成了条件性敲除小鼠，其中受体在早期成骨细胞分化期间正常存在，但在成骨细胞成熟时失活。这些动物的骨老化与对照动物观察到的相似。相比之下，条件性 ERRαKO 小鼠对卵巢切除引起的骨丢失完全具有抗性。我们得出结论，ERRα 对成骨细胞谱系的晚期（成熟）而非早期（分化）负向作用导致雌激素缺乏时观察到的骨密度降低。
