An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/β-Catenin and Erk1/2-MAPK Pathways

被引:44
作者
Hu, Hongyang [1 ,2 ]
Chen, Min [3 ]
Dai, Guangzu [2 ]
Du, Guoqing [2 ]
Wang, Xuezong [2 ]
He, Jie [2 ]
Zhao, Yongfang [2 ]
Han, Dapeng [1 ]
Cao, Yuelong [1 ,2 ]
Zheng, Yuxin [1 ,2 ]
Ding, Daofang [1 ,2 ]
机构
[1] Shanghai Univ TCM, Guanghua Integrat Med Hosp, Shanghai Acad Chinese Med Sci, Inst Arthrit Res, Shanghai 200052, Peoples R China
[2] Shanghai Univ TCM, Shuguang Hosp, Shis Ctr Orthoped & Traumatol, Shanghai 200052, Peoples R China
[3] Shanghai Univ TCM, Shuguang Hosp, Reprod Med Ctr, Shanghai 200052, Peoples R China
基金
中国国家自然科学基金;
关键词
Osthole; Mesenchymal stem cells; Proliferation; Osteogenic differentiation; Signaling pathway; MESENCHYMAL STEM-CELLS; CANCER A549 CELLS; SIGNALING PATHWAY; STROMAL CELLS; EXPRESSION; PROMOTES; PI3K/AKT; APOPTOSIS; ARREST;
D O I
10.1159/000445590
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Elockground/Aims: Bone marrow-derived mesenchymal stem cells (MSCs) are responsible for new bone formation during adulthood. Accumulating evidences showed that Osthole promotes the osteogenic differentiation in primary osteoblasts. The aim of this study was to investigate whether Osthole exhibits a potential to stimulate the osteogenic differentiation of MSCs and the underlying mechanism. Methods: MSCs were treated with a gradient concentration of Osthole (6.25 mu M, 12.5 mu M, and 25 mu M). Cell proliferation was assessed by western blotting with the proliferating cell nuclear antigen (PCNA) and Cyclin D1 antibodies, fluorescence activated cell sorting (FACS), and cell counting kit 8 (CCK8). MSCs were cultured in osteogenesis-induced medium for one or two weeks. The osteogenic differentiation of MSCs was estimated by Alkaline Phosphatase (ALP) staining, Alizarin red staining, Calcium influx, and quantitative PCR (qPCR). The underlying mechanism of Osthole-induced osteogenesis was further evaluated by western blotting with antibodies in Wnt/beta-catenin, PI3K/Akt, BMPs/smad1/5/8, and MAPK signaling pathways. Results: Osthole inhibited proliferation of rat MSCs in a dose-dependent manner. Osthole suppressed osteogenic differentiation of rat MSCs by down-regulating the activities of Wnt/beta-catenin and Erk1/2-MAPK signaling. Conclusions: Osthole inhibits the proliferation and osteogenic differentiation of rat MSCs, which might be mediated through blocking the Wnt/beta-catenin and Frk1/2-MAPK signaling pathways. (C) 2016 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:2375 / 2388
页数:14
相关论文
共 39 条
[1]
Short-term effects of calcium ions on the apoptosis and onset of mineralization of human dental pulp cells in vitro and in vivo [J].
An, Shaofeng ;
Gao, Yan ;
Huang, Yihua ;
Jiang, Xiaoqiong ;
Ma, Ke ;
Ling, Junqi .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2015, 36 (01) :215-221
[2]
Promotion of human mesenchymal stem cell osteogenesis by PI3-kinase/Akt signaling, and the influence of caveolin-1/cholesterol homeostasis [J].
Baker, Natasha ;
Sohn, Jihee ;
Tuan, Rocky S. .
STEM CELL RESEARCH & THERAPY, 2015, 6
[3]
Phosphate is a specific signal for induction of osteopontin gene expression [J].
Beck, GR ;
Zerler, B ;
Moran, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (15) :8352-8357
[4]
The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine [J].
Bianco, Paolo ;
Cao, Xu ;
Frenette, Paul S. ;
Mao, Jeremy J. ;
Robey, Pamela G. ;
Simmons, Paul J. ;
Wang, Cun-Yu .
NATURE MEDICINE, 2013, 19 (01) :35-42
[5]
Chen J, 2013, TISSUE ENG PART B-RE, V19, P516, DOI [10.1089/ten.teb.2012.0672, 10.1089/ten.TEB.2012.0672]
[6]
An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells [J].
Chen, Qing ;
Shou, Peishun ;
Zhang, Liying ;
Xu, Chunliang ;
Zheng, Chunxing ;
Han, Yanyan ;
Li, Wenzhao ;
Huang, Yin ;
Zhang, Xiaoren ;
Shao, Changshun ;
Roberts, Arthur I. ;
Rabson, Arnold B. ;
Ren, Guangwen ;
Zhang, Yanyun ;
Wang, Ying ;
Denhardt, David T. ;
Shi, Yufang .
STEM CELLS, 2014, 32 (02) :327-337
[7]
NBM-T-BMX-OS01, an Osthole Derivative, Sensitizes Human Lung Cancer A549 Cells to Cisplatin through AMPK-Dependent Inhibition of ERK and Akt Pathway [J].
Chen, Tian-Jun ;
Zhou, Yue-Fei ;
Ning, Jie-Juan ;
Yang, Tian ;
Ren, Hui ;
Li, Yang ;
Zhang, Shuo ;
Chen, Ming-Wei .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 36 (03) :893-906
[8]
Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation [J].
Choudhery, Mahmood S. ;
Badowski, Michael ;
Muise, Angela ;
Pierce, John ;
Harris, David T. .
JOURNAL OF TRANSLATIONAL MEDICINE, 2014, 12
[9]
Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways [J].
Ding, Daofang ;
Wei, Songpu ;
Song, Yi ;
Li, Linghui ;
Du, Guoqing ;
Zhan, Hongsheng ;
Cao, Yuelong .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2013, 32 (06) :1751-1760
[10]
Expression of core-binding factor α1 and osteocalcin in fluoride-treated fibroblasts and osteoblasts [J].
Duan, Xiaoqin ;
Xu, Hui ;
Wang, Ying ;
Wang, Huan ;
Li, Guangsheng ;
Jing, Ling .
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, 2014, 28 (03) :278-283