Effects of Canonical NF-κB Signaling Pathway on the Proliferation and Odonto/Osteogenic Differentiation of Human Stem Cells from Apical Papilla

被引:20
作者
Li, Junjun [1 ]
Yan, Ming [2 ]
Wang, Zilu [1 ]
Jing, Shuanglin [2 ]
Li, Yao [1 ]
Liu, Genxia [1 ]
Yu, Jinhua [1 ,2 ]
Fan, Zhipeng [3 ,4 ]
机构
[1] Nanjing Med Univ, Inst Stomatol, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Sch Stomatol, Endodont Dept, Nanjing 210029, Jiangsu, Peoples R China
[3] Capital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing 100050, Peoples R China
[4] Capital Med Univ, Sch Stomatol, Mol Lab Gene Therapy & Tooth Regenerat, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Beijing 100050, Peoples R China
基金
中国国家自然科学基金;
关键词
HIGHLY SELECTIVE INHIBITOR; TNF-ALPHA PROMOTES; GROWTH-FACTOR; DENTAL-PULP; OSTEOGENIC DIFFERENTIATION; ACTIVATION; MINERALIZATION; KINASE; TRANSCRIPTION; REGENERATION;
D O I
10.1155/2014/319651
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background Information. NF-kappa B signaling pathway plays a complicated role in the biological functions of mesenchymal stem cells. However, the effects of NF-kappa B pathway on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) remain unclear. The present study was designed to evaluate the effects of canonical NF-kappa B pathway on the osteo/odontogenic capacity of SCAPs in vitro. Results. Western blot results demonstrated that NF-kappa B pathway in SCAPs was successfully activated by TNF-alpha or blocked by BMS-345541. NF-kappa B pathway-activated SCAPs presented a higher proliferation activity compared with control groups, as indicated by dimethyl-thiazol-diphenyl tetrazoliumbromide assay (MTT) and flowcytometry assay (FCM). Wound scratch assay revealed that NF-kappa B pathway-activated SCAPs presented an improved migration capacity, enhanced alkaline phosphatase (ALP) activity, and upregulated mineralization capacity of SCAPs, as compared with control groups. Meanwhile, the odonto/osteogenic markers (ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, OPN/OPN, BSP/BSP, DSPP/DSP, and DMP-1/DMP-1) in NF-kappa B pathway-activated SCAPs were also significantly upregulated as compared with control groups at both protein and mRNA levels. However, NF-kappa B pathway-inhibited SCAPs exhibited a lower proliferation/migration capacity, and decreased odonto/osteogenic ability in comparison with control groups. Conclusion. Our findings suggest that classical NF-kappa B pathway plays a paramount role in the proliferation and committed differentiation of SCAPs.
引用
收藏
页数:12
相关论文
共 38 条
[1]   Characteristics and osteogenic differentiation of stem/progenitor cells in the human dental follicle analyzed by gene expression profiling [J].
Aonuma, H. ;
Ogura, N. ;
Takahashi, K. ;
Fujimoto, Y. ;
Iwai, S. ;
Hashimoto, H. ;
Ito, K. ;
Kamino, Y. ;
Kondoh, T. .
CELL AND TISSUE RESEARCH, 2012, 350 (02) :317-331
[2]   The two NF-κB activation pathways and their role in innate and adaptive immunity [J].
Bonizzi, G ;
Karin, M .
TRENDS IN IMMUNOLOGY, 2004, 25 (06) :280-288
[3]   BMS-345541 is a highly selective inhibitor of IκB kinase that binds at an allosteric site of the enzyme and blocks NF-κB-dependent transcription in mice [J].
Burke, JR ;
Pattoli, MA ;
Gregor, KR ;
Brassil, PJ ;
MacMaster, JF ;
McIntyre, KW ;
Yang, XX ;
Iotzova, VS ;
Clarke, W ;
Strnad, J ;
Qiu, YP ;
Zusi, FC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1450-1456
[4]   Notch signalling pathway in tooth development and adult dental cells [J].
Cai, X. ;
Gong, P. ;
Huang, Y. ;
Lin, Y. .
CELL PROLIFERATION, 2011, 44 (06) :495-507
[5]   Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers [J].
Cao, Dong-Xing ;
Li, Zhi-Jie ;
Jiang, Xiao-Ou ;
Lum, Yick Liang ;
Khin, Ester ;
Lee, Nikki P. ;
Wu, Guo-Hao ;
Luk, John M. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2012, 18 (30) :3923-3930
[6]   NF-κB inhibits osteogenic differentiation of mesenchymal stem cells by promoting β-catenin degradation [J].
Chang, Jia ;
Liu, Fei ;
Lee, Min ;
Wu, Benjamin ;
Ting, Kang ;
Zara, Janette N. ;
Soo, Chia ;
Al Hezaimi, Khalid ;
Zou, Weiping ;
Chen, Xiaohong ;
Mooney, David J. ;
Wang, Cun-Yu .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (23) :9469-9474
[7]  
Chen F, 1999, CLIN CHEM, V45, P7
[8]   Runx2, Osx, and Dspp in Tooth Development [J].
Chen, S. ;
Gluhak-Heinrich, J. ;
Wang, Y. H. ;
Wu, Y. M. ;
Chuang, H. H. ;
Chen, L. ;
Yuan, G. H. ;
Dong, J. ;
Gay, I. ;
MacDougall, M. .
JOURNAL OF DENTAL RESEARCH, 2009, 88 (10) :904-909
[9]  
Chopra Hitesh, 2013, Dent Res J (Isfahan), V10, P421
[10]   The Ectodysplasin and NFκB signalling pathways in odontogenesis [J].
Courtney, JM ;
Blackburn, J ;
Sharpe, PT .
ARCHIVES OF ORAL BIOLOGY, 2005, 50 (02) :159-163