Fluid shear stress inhibits TNF-α-induced osteoblast apoptosis via ERK5 signaling pathway

Biochemical and Biophysical Research Communications
Geng BinXia Yayi

Abstract

Fluid shear stress (FSS) is a potent mechanical stimulus and prevents cells from TNF-a-induced apoptosis. Recently, Extracellular-signal-regulated kinase 5 (ERK5) has been found to be involved in regulation of cell survival. However, little is known about the role of ERK5 signaling pathway in FSS-mediated anti-apoptotic effects in osteoblast. In this study, we show that FSS blocks TNF-a-induced apoptosis of MC3T3-E1 cells via ERK5 signaling pathway. We found that physiological FSS for 1 h significantly decreased TNF-α-induced MC3T3-E1 cells apoptosis. After inhibition of ERK5 activity by XMD8-92, a highly-selective inhibitor of ERK5 activity, the ability of FSS to inhibit TNF-α induced apoptosis was significantly decreased. Analysis of anti-apoptotic mechanisms indicated that exposure of MC3T3-E1 cells to FSS for 1 h increased phosphorylation of Bad and inhibited caspase-3 activity. After treatment with XMD8-92, phosphorylation of Bad by FSS was significantly blocked, but caspase-3 activity was increased. In summary, these findings indicated that FSS inhibits TNF-α-mediated signaling events in osteoblast by a mechanism dependent on activation of ERK5, and Bad is a crucial downstream target for ERK5. Those results implied that E...Continue Reading

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Citations

Oct 18, 2016·Frontiers in Physiology·Bipradas RoyHugh M Fentress
Jun 22, 2017·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Liwen ZhengHuaying Zhou
Apr 4, 2018·Connective Tissue Research·Ning DingYayi Xia
Jul 12, 2021·Research in Veterinary Science·Shilei HuangZhenhui Song

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