title: EGFR trans-activation mediates pleiotrophin-induced activation of Akt and Erk in cultured osteoblasts.
abstract: 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 Erk 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.
authors.affiliation: The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, North Hai-er-xiang Road 6, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Fan
authors.affiliation: The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, North Hai-er-xiang Road 6, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, North Hai-er-xiang Road 6, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yuan
authors.affiliation: The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, North Hai-er-xiang Road 6, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Zhu
authors.affiliation: The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, North Hai-er-xiang Road 6, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Xu
authors.affiliation: The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, North Hai-er-xiang Road 6, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, North Hai-er-xiang Road 6, Nantong 226001, Jiangsu, People's Republic of China. Electronic address: zhimingcuiorth@163.com.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Cui
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases; D051379:Mice; D010006:Osteoblasts / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C066845:pleiotrophin; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Akt/Erk signalings; EGFR; Osteoblasts and bone growth; Pleiotrophin