Opposite Function of ERα and ERβ in Controlling 17β-Estradiol-mediated Osteogenesis in Osteoblasts.
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.
Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, ChangSha, Hunan, China.
Yu-Xiang
YX
Wang
Xiangya Stomatology Hospital of Central South University, ChangSha, Hunan, China.
Min
M
Li
Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, ChangSha, Hunan, China. Electronic address: zhanghongqi9996@sina.com.
Hong-Qi
HQ
Zhang
Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, ChangSha, Hunan, China.
Ming-Xing
MX
Tang
Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, ChangSha, Hunan, China.
Chao-Feng
CF
Guo
Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, ChangSha, Hunan, China.
Ang
A
Deng
Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, ChangSha, Hunan, China.
Yong
Y
Chen
Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, ChangSha, Hunan, China.
Li-Ge
LG
Xiao
D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D053244:Osteoprotegerin; D053245:RANK Ligand; C493709:RUNX2 protein, human; C505688:TNFSF11 protein, human; D016212:Transforming Growth Factor beta; D004958:Estradiol; D007334:Insulin-Like Growth Factor I
Estrogen receptor; Osteoblasts; Osteogenesis; Signaling pathway