EGFR trans-activation mediates pleiotrophin-induced activation of Akt and Erk in cultured osteoblasts

被引：42

作者：

Fan, Jian-bo ^{[1
]}

Liu, Wei ^{[1
]}

Yuan, Kun ^{[1
]}

Zhu, Xin-hui ^{[1
]}

Xu, Da-wei ^{[1
]}

Chen, Jia-jia ^{[1
]}

Cui, Zhi-ming ^{[1
]}

机构：

[1] Nantong Univ, Affiliated Hosp 2, Dept Orthopaed, Nantong 226001, Jiangsu, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2014年 / 447卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Pleiotrophin; EGFR; Akt/Erk signalings; Osteoblasts and bone growth; ANAPLASTIC LYMPHOMA KINASE; DIVERSE FUNCTIONS; BONE-FORMATION; RECEPTOR; PROTEIN; ANGIOGENESIS; MECHANISMS; EXPRESSION; PROLIFERATION; OSTEONECROSIS;

D O I：

10.1016/j.bbrc.2014.04.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Pleiotrophin (Ptn) plays an important role in bone growth through regulating osteoblasts' functions. The underlying signaling mechanisms are not fully understood. In the current study, we found that Ptn induced heparin-binding epidermal growth factor (HB-EGF) release to trans-activate EGF-receptor (EGFR) in both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, Ptn activated Akt and Erk signalings in cultured osteoblasts. The EGFR inhibitor AG1478 as well as the monoclonal antibody against HB-EGF (anti-HB-EGF) significantly inhibited Ptn-induced EGFR activation and Akt and Erk phosphorylations in MC3T3-E1 cells and primary osteoblasts. Further, EGFR siRNA depletion or dominant negative mutation suppressed also Akt and Eric activation in MC3T3-E1 cells. Finally, we observed that Ptn increased alkaline phosphatase (ALP) activity and inhibited dexamethasone (Dex)-induced cell death in both MC3T3-E1 cells and primary osteoblasts, such effects were alleviated by AG1478 or anti-HB-EGF. Together, these results suggest that Ptn-induced Akt/Erk activation and some of its pleiotropic functions are mediated by EGFR trans-activation in cultured osteoblasts. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：425 / 430

页数：6

共 37 条

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