PMID- 28554841 OWN - NLM STAT- MEDLINE DCOM- 20170925 LR - 20181202 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 489 IP - 3 DP - 2017 Jul 29 TI - ERK1/2 signaling mediated naringin-induced osteogenic differentiation of immortalized human periodontal ligament stem cells. PG - 319-325 LID - S0006-291X(17)31023-9 [pii] LID - 10.1016/j.bbrc.2017.05.130 [doi] AB - Periodontal ligament stem cells (PDLSCs) are promising tools for the investigations of cell differentiation and bone regeneration. However, the limited life span significantly restricts their usefulness. In this study, we established an immortalized PDLSC cell line by the introduction of Bmi1 (PDLSC-Bmi1). Several genes related to cell cycle, cell replication and stemness were found to be changed with the overexpression of Bmi1. Compared with primary PDLSCs, the immortalized cells had a slower aging rate, maintained in a proliferative state without crisis for more than 30 passages, and retained the molecular markers and biological functions of primary ones. Using the PDLSC-Bmi1, we confirmed the promotive effect of naringin on osteogenesis. Naringin promoted the osteogenic differentiation of PDLSC-Bmi1 manifested as the increased activity of alkaline phosphatase (ALP), expression of the runt-related transcription factor 2 (Runx2) and osteocalcin (OCN), and formation of mineralized nodules. In addition, the extracellular regulated protein kinases (ERK) 1/2 was found to be activated by naringin, and the ERK1/2 specific inhibitor significantly inhibited naringin-induced osteogenic differentiation in PDLSC-Bmi1. Our results indicated that the overexpression of Bmi1 extended the life span of PDLSCs without perturbing their biological functions, and that naringin promoted the osteogenesis of PDLSC-Bmi1 at least partially through the ERK1/2 signaling pathway. CI - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Wei, Kai AU - Wei K AD - Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China; Medical College, Nankai University, Tianjin 300071, China. FAU - Xie, Yuansheng AU - Xie Y AD - Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China. Electronic address: xieyuansn@hotmail.com. FAU - Chen, Tianyu AU - Chen T AD - Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China. FAU - Fu, Bo AU - Fu B AD - Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China. FAU - Cui, Shaoyuan AU - Cui S AD - Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China. FAU - Wang, Yan AU - Wang Y AD - Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China. FAU - Cai, Guangyan AU - Cai G AD - Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China. FAU - Chen, Xiangmei AU - Chen X AD - Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China. LA - eng PT - Journal Article DEP - 20170526 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Flavanones) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - N7TD9J649B (naringin) SB - IM MH - Adolescent MH - Adult MH - Cell Differentiation/drug effects MH - Female MH - Flavanones/chemistry/*pharmacology MH - HEK293 Cells MH - Humans MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Mesenchymal Stem Cells/*cytology/*drug effects MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Osteogenesis/*drug effects MH - Periodontal Ligament/*cytology MH - Young Adult OTO - NOTNLM OT - ERK OT - Immortalization OT - Naringin OT - Osteogenesis OT - Periodontal ligament stem cell EDAT- 2017/05/31 06:00 MHDA- 2017/09/26 06:00 CRDT- 2017/05/31 06:00 PHST- 2017/03/17 00:00 [received] PHST- 2017/05/23 00:00 [accepted] PHST- 2017/05/31 06:00 [pubmed] PHST- 2017/09/26 06:00 [medline] PHST- 2017/05/31 06:00 [entrez] AID - S0006-291X(17)31023-9 [pii] AID - 10.1016/j.bbrc.2017.05.130 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2017 Jul 29;489(3):319-325. doi: 10.1016/j.bbrc.2017.05.130. Epub 2017 May 26.