High glucose impaired estrogen receptor alpha signaling via β-catenin in osteoblastic MC3T3-E1

作者：Wang, Rui; Gao, Dong; Zhou, Yin; Chen, Lu; Luo, Bin; Yu, Yanrong; Li, Hao; Hu, Jiawei; Huang, Qiren; He, Ming; Peng, Weijie^*; Luo, Dan^*

来源：Journal of Steroid Biochemistry and Molecular Biology, 2017, 174: 276-283.

DOI：10.1016/j.jsbmb.2017.10.008

• High glucose
• Estrogen receptor
• Osteoblast
• beta-catenin

Diabetic Mellitus is a risk factor for osteoporosis. It has been suggested that altered estrogen or estrogen receptor alpha/beta (ER alpha/beta) signaling may be involved in diabetic osteoporosis. The present study is to investigate the effects of high glucose on ER alpha/beta signaling in osteoblastic MC3T3-E1 and how the altered signaling of ER alpha/beta affect osteoblastic bone formation. ER alpha/beta signaling was demonstrated as ER alpha/beta protein expression (Western Blotting) and ER transcription activity (Luciferase Reporter assays). Proliferation (WSK-1 assaying), differentiation (ALP staining) and mineralization (Alizalard Red staining) of MC3T3-E1 were examined to evaluate bone formation function. It has been found that high glucose increased ER alpha/beta expression dose-dependently and time-dependently, but high glucose (33 mM) decreased ER alpha transcription activity. 17 beta-estradiol increased the ER alpha/beta expression dose-dependently in normal medium, but decreased the ER alpha/beta expression dose-dependently in medium with high glucose (33 mM). High glucose decreased bone formation and also decreased the osteogenic effects of 17 beta-estTadiol (10(-8) M). High glucose decreased beta-catenin expression dose-dependently and time-dependently. LiCl, an inhibitor of beta-catenin degradation, decreased ER alpha expression but increased ER alpha transcription activity. When compared with high glucose treatment, LiC1 (5 mM) increased ALP activity and calcified nodes. Besides, high glucose also decreased the protein expression PI-3 K, pAKT/AKT, GSK-3 beta. In conclusion, the present study suggested that high glucose may impair ER alpha transcription activity by inhibiting beta-catenin signaling in osteoblastic MC3T3-E1, leading decreased bone formation ligand-dependently or ligand-independently.

• 出版日期2017-11
• 单位南昌大学