Hepatocyte Growth Factor Increases Osteopontin Expression in Human Osteoblasts through PI3K, Akt, c-Src, and AP-1 Signaling Pathway

被引:37
作者
Chen, Hsien-Te [1 ,2 ,3 ]
Tsou, Hsi-Kai [3 ,4 ,5 ]
Chang, Chia-Hao [6 ]
Tang, Chih-Hsin [7 ,8 ]
机构
[1] China Med Univ, Coll Chinese Med, Sch Chinese Med, Taichung, Taiwan
[2] China Med Univ Hosp, Dept Orthoped Surg, Taichung, Taiwan
[3] Feng Chia Univ, Dept Mat Sci & Engn, Taichung 40724, Taiwan
[4] Taichung Vet Gen Hosp, Dept Neurosurg, Taichung, Taiwan
[5] Jen Teh Jr Coll Med Nursing & Management, Ctr Gen Educ, Miaoli Cty, Taiwan
[6] Chang Hwa Hosp, Dept Orthoped Surg, Dept Hlth Execut Yuan, Chang Hwa Cty, Taiwan
[7] China Med Univ, Sch Med, Dept Pharmacol, Taichung, Taiwan
[8] China Med Univ, Grad Inst Basic Med Sci, Taichung, Taiwan
来源
PLOS ONE | 2012年 / 7卷 / 06期
关键词
PARTIAL-PURIFICATION; GENE-EXPRESSION; CELLS; ACTIVATION; KINASE; SURVIVAL; BONE; DIFFERENTIATION; ASSOCIATION; FIBROBLAST;
D O I
10.1371/journal.pone.0038378
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Hepatocyte growth factor (HGF) has been demonstrated to stimulate osteoblast proliferation and participated bone remodeling. Osteopontin (OPN) is a secreted phosphoglycoprotein that belongs to the SIBLING family and is present during bone mineralization. However, the effects of HGF on OPN expression in human osteoblasts are large unknown. Methodology/Principal Findings: Here we found that HGF induced OPN expression in human osteoblasts dose-dependently. HGF-mediated OPN production was attenuated by c-Met inhibitor and siRNA. Pretreatment of osteoblasts with PI3K inhibitor (Ly294002), Akt inhibitor, c-Src inhibitor (PP2), or AP-1 inhibitor (curcumin) blocked the potentiating action of HGF. Stimulation of osteoblasts with HGF enhanced PI3K, Akt, and c-Src activation. In addition, incubation of cells with HGF also increased c-Jun phosphorylation, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the OPN promoter. HGF-mediated AP-1-luciferase activity and c-Jun binding to the AP-1 element was reduced by c-Met inhibitor, Ly294002, Akt inhibitor, and PP2. Conclusions/Significance: Our results suggest that the interaction between HGF and c-Met increases OPN expression in human osteoblasts via the PI3K, Akt, c-Src, c-Jun, and AP-1 signaling pathway.
引用
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页数:11
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