Selective regulation of osteoblastic OPG and RANKL by dehydroepiandrosterone through activation of the estrogen receptor β-mediated MAPK signaling pathway.

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme
Y-D WangX-P Wan

Abstract

The aim of the work was to investigate the differential regulation by dehydroepiandrosterone (DHEA) of the osteoblastic production via the estrogen receptor beta (ER β)-mediated signaling pathway. Having developed hMG63-ER β cells and hMG63-shER β cells, we analyzed the regulation by DHEA of human osteoblastic viability, the receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), and the differential expression of ER β, ER α, or p-ERK1/2 (extracellular signal-regulated kinase) in hMG63, hMG63-shER β, and hMG63-ER β cells pretreated with or without U0126, flutamide, and ICI 182780, followed by DHEA culture. When the level of ER β was high, DHEA (10 - 7 mol/l) could effectively amplify the proliferation and inhibit the etoposide-induced apoptosis of hMG63 cells (p<0.01 and p<0.05, respectively), which was blocked by U0126. When the expression of ER β was silenced, DHEA could not significantly improve the viability of hMG63. In the presence of ER β, DHEA activated the pERK1/2-MAPK signaling pathway but not p38 and JNK. Besides, the regulation of p-ERK1/2 upon DHEA treatment was mainly modulated by ER β instead of androgen receptor and ER α. The secretion of OPG was declined following the silence of ER ...Continue Reading

Citations

Apr 6, 2013·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Duangrat TantikanlayapornHarry C Blair
Sep 13, 2015·Biochemical and Biophysical Research Communications·Ting WangChaoyin Jiang
Feb 15, 2015·Mechanisms of Ageing and Development·Ping Kwan
Feb 20, 2013·International Journal of Cancer. Journal International Du Cancer·Li-Sha AiYu Hu
Nov 7, 2019·Frontiers in Endocrinology·María Virginia GentiliniMaría Victoria Delpino

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