caa a22 4500 606235027 CHVBK 20210128101240.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2210-4 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2210-4 EGFR-AKT-mTOR activation mediates epiregulin-induced pleiotropic functions in cultured osteoblasts [Elektronische Daten] [Jian-bo Fan, Wei Liu, Xin-hui Zhu, Kun Yuan, Da-wei Xu, Jia-jia Chen, Zhi-ming Cui] Epidermal growth factor (EGF) receptor (EGFR) emerges as an essential molecule for the regulating of osteoblast cellular functions. In the current study, we explored the effect of epiregulin, a new EGFR ligand, on osteoblast functions in vitro, and studied the underlying mechanisms. We found that epiregulin-induced EGFR activation in both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, epiregulin activated AKT-mammalian target of rapamycin (mTOR) and Erk-mitogen-activated protein kinase (MAPK) signalings in cultured osteoblasts, which were blocked by EGFR inhibitor AG1478 or monoclonal antibody against EGFR (anti-EGFR). Further, in primary and MC3T3-E1 osteoblasts, epiregulin promoted cell proliferation and increased alkaline phosphatase activity, while inhibiting dexamethasone (Dex)-induced cell death. Such effects by epiregulin were largely inhibited by AG1478 or anti-EGFR. Notably, AKT-mTOR inhibitors, but not Erk inhibitors, alleviated epiregulin-induced above pleiotropic functions in osteoblasts. Meanwhile, siRNA depletion of Sin1, a key component of mTOR complex 2 (mTORC2), also suppressed epiregulin-exerted effects in MC3T3-E1 cells. Together, these results suggest that epiregulin-induced pleiotropic functions in cultured osteoblasts are mediated through EGFR-AKT-mTOR signalings. Springer Science+Business Media New York, 2014 Epiregulin nationallicence EGFR nationallicence AKT/mTOR signalings nationallicence Osteoblasts nationallicence ALP : Alkaline phosphatase nationallicence EGF : Epidermal growth factor nationallicence Dex : Dexamethasone nationallicence mTOR : Mammalian target of rapamycin nationallicence S6K1 : Ribosomal S6 kinase 1 nationallicence Fan Jian-bo The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut Liu Wei The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut Zhu Xin-hui The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut Yuan Kun The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut Xu Da-wei The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut Chen Jia-jia The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut Cui Zhi-ming The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 105-113 0300-8177 398:1-2<105 2015 398 11010 https://doi.org/10.1007/s11010-014-2210-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2210-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fan Jian-bo The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut NATIONALLICENCE 700 1- Liu Wei The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut NATIONALLICENCE 700 1- Zhu Xin-hui The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut NATIONALLICENCE 700 1- Yuan Kun The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut NATIONALLICENCE 700 1- Xu Da-wei The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut NATIONALLICENCE 700 1- Chen Jia-jia The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut NATIONALLICENCE 700 1- Cui Zhi-ming The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, 6 North Hai-er-xiang Road, 226001, Nantong, Jiangsu, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 105-113 0300-8177 398:1-2<105 2015 398 11010