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EGFR trans-activation mediates pleiotrophin-induced activation of Akt and Erk in cultured osteoblasts.
Fan, Jian-Bo; Liu, Wei; Yuan, Kun; Zhu, Xin-Hui; Xu, Da-Wei; Chen, Jia-Jia; Cui, Zhi-Ming.
Afiliação
  • Fan JB; 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.
  • Liu W; 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.
  • Yuan K; 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.
  • Zhu XH; 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.
  • Xu DW; 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.
  • Chen JJ; 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.
  • Cui ZM; 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.
Biochem Biophys Res Commun ; 447(3): 425-30, 2014 May 09.
Article em En | MEDLINE | ID: mdl-24727451
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoblastos / Proteínas Proto-Oncogênicas c-akt / Receptores ErbB Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoblastos / Proteínas Proto-Oncogênicas c-akt / Receptores ErbB Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article