雌激素受体 ERα 和 ERβ 对成骨细胞中 17β-雌二醇介导的成骨作用的相反作用。

Opposite Function of ERα and ERβ in Controlling 17β-Estradiol-mediated Osteogenesis in Osteoblasts.

机构信息

Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, ChangSha, Hunan, China.

Xiangya Stomatology Hospital of Central South University, ChangSha, Hunan, China.

出版信息

Arch Med Res. 2016 May;47(4):255-61. doi: 10.1016/j.arcmed.2016.07.002.

DOI:10.1016/j.arcmed.2016.07.002

PMID:27664484

Abstract

Estrogen receptor plays critical roles in osteogenesis but the underlying mechanism remains unclear. In order to determine the effect of ERα and ERβ on several critical factors in regulating osteogenesis in human osteoblasts. Cell based assy, RT-PCR and immunoblot analyses were used in the research. Both RT-PCR and immunoblot showed that gene expression of OPG, MBP2, TGF-β, RUNX2, IGF-1 was significantly reduced while expression of RANKL was drastically increased after shRNA-based depletion of ERα in MG-63 osteoblasts. Surprisingly, 17β-estradiol (E2) treatment led to remarkably reduced RANKL compared with that in E2 untreated cells. In contrast, ERβ plays an opposite role in regulating gene expression of OPG, MBP2, TGF-β, RUNX2, IGF-1 and RANKL. However, double depletion of ERα and ERβ could not rescue the gene expression of these factors in vitro. Our results provide a novel mechanism of estrogen receptor in controlling osteogenesis in human cells as well as a potential clinic therapeutic target in human osteoporosis.

摘要

雌激素受体在成骨中发挥关键作用，但潜在机制尚不清楚。为了确定 ERα 和 ERβ 对调节人成骨细胞成骨的几个关键因素的影响。本研究采用细胞基础测定、RT-PCR 和免疫印迹分析。RT-PCR 和免疫印迹均显示，shRNA 敲低 MG-63 成骨细胞中的 ERα 后，OPG、MBP2、TGF-β、RUNX2、IGF-1 的基因表达明显降低，而 RANKL 的表达则急剧增加。令人惊讶的是，与未经 E2 处理的细胞相比，17β-雌二醇（E2）处理导致 RANKL 显著减少。相比之下，ERβ 在调节 OPG、MBP2、TGF-β、RUNX2、IGF-1 和 RANKL 的基因表达中发挥相反的作用。然而，双重敲低 ERα 和 ERβ 并不能挽救这些因子在体外的基因表达。我们的结果为雌激素受体在控制人细胞成骨中的作用提供了一种新的机制，以及人类骨质疏松症的潜在临床治疗靶点。