Oncotarget

Research Papers:

Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone

Weidong Liu, Li Mao, Feng Ji _, Fengli Chen, Shouguo Wang and Yue Xie

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:2594-2603. https://doi.org/10.18632/oncotarget.13732

Metrics: PDF 2461 views  |   HTML 3015 views  |   ?  


Abstract

Weidong Liu1,*, Li Mao2,*, Feng Ji1, Fengli Chen3, Shouguo Wang1, Yue Xie1

1Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

2Department of Endocrinology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

3Clinical Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

*Co-first authors

Correspondence to:

Feng Ji, email: [email protected]

Keywords: icariside II, dexamethasone, EGFR-Akt, Nrf2 signaling, oxidative stress

Received: November 07, 2016     Accepted: November 21, 2016     Published: December 01, 2016

ABSTRACT

The potential effect of icariside II on dexamethasone-induced osteoblast cell damages was evaluated here. In MC3T3-E1 osteoblastic cells and the primary murine osteoblasts, co-treatment with icariside II dramatically attenuated dexamethasone- induced cell death and apoptosis. Icariside II activated Akt signaling, which is required for its actions in osteoblasts. Akt inhibitors (LY294002, perifosine and MK-2206) almost abolished icariside II-induced osteoblast cytoprotection against dexamethasone. Further studies showed that icariside II activated Nrf2 signaling, downstream of Akt, to inhibit dexamethasone-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary osteoblasts. On the other hand, Nrf2 shRNA knockdown inhibited icariside II-induced anti-dexamethasone cytoprotection in MC3T3-E1 cells. Finally, we showed that icariside II induced heparin-binding EGF (HB-EGF) production and EGFR trans-activation in MC3T3-E1 cells. EGFR inhibition, via anti-HB-EGF antibody, EGFR inhibitor AG1478 or EGFR shRNA knockdown, almost blocked icariside II-induced Akt-Nrf2 activation in MC3T3-E1 cells. Collectively, we conclude that icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone. Icariside II might have translational value for the treatment of dexamethasone-associated osteoporosis/osteonecrosis.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 13732