TGF-β2 and TGF-β1 differentially regulate the odontogenic and osteogenic differentiation of mesenchymal stem cells

被引:30
作者
Li, Jingzhi [1 ,2 ]
Ge, Lihong [1 ]
Zhao, Yuming [1 ]
Zhai, Yue [3 ]
Rao, Nanquan [4 ]
Yuan, Xiaojing [1 ]
Yang, Jie [1 ]
Li, Jing [5 ]
Yu, Shi [1 ,6 ]
机构
[1] Peking Univ Sch & Hosp Stomatol, Dept Pediat Dent, Beijing, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Coll Stomatol, Dept Pediat Dent,Sch Med, Shanghai, Peoples R China
[3] Capital Med Univ, Beijing Childrens Hosp, Dept Stomatol, Beijing, Peoples R China
[4] Kunming Med Univ, Hosp Stomatol, Dept Dent Res, Kunming, Peoples R China
[5] China Japan Friendship Hosp, Dent Med Ctr, Beijing, Peoples R China
[6] Peking Univ Sch & Hosp Stomatol, Dept Pediat Dent, Zhongguancun South Ave 22, Beijing 100081, Peoples R China
关键词
TGF-beta; 1; 2; Stem cell from apical papilla; Bone marrow stem cell; Odontogenic differentiation; Osteogenic differentiation; T-BETA-RII; APICAL PAPILLA; DENTAL-PULP; TRANSFORMING GROWTH-FACTOR-BETA-1; PULP/DENTIN REGENERATION; TISSUE FORMATION; GENE-EXPRESSION; GROWTH; OSTEOBLASTS; SCAFFOLD;
D O I
10.1016/j.archoralbio.2022.105357
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Objective: To explore the effects of transforming growth factor -beta 2 (TGF-beta 2) and TGF-beta 1 on the odontogenic and osteogenic differentiation of mesenchymal stem cells (MSCs). Design: We used lentiviral transduction to knock down TGF-beta 1 or TGF-beta 2 in stem cells from dental apical papilla (SCAPs), and to generate bone marrow mesenchymal stem cells (BMSCs) with overexpression of TGF-beta 1 or TGF-beta 2. We investigated the odontogenic and osteogenic differentiation abilities of these transductants in vitro and in vivo. Results: In vitro, TGF-beta 2 knockdown in SCAPs reduced the expression of odontoblast-related markers DSPP and DMP-1, and increased the expression of osteoblast-related markers OCN and RUNX-2. Conversely, TGF-beta 1 knockdown had the opposite effects. TGF-beta 2 overexpression promoted expression of odontoblast-related markers in BMSCs at early differentiation, but inhibited the expression of odontoblast-related markers at later stages. TGF-beta 2 overexpression attenuated expression of osteogenic-related markers in BMSCs, while TGF-beta 1 over expression enhanced odontoblast-related and osteoblast-related markers. SCAP or BMSC transductants were transplanted underneath kidneys in vivo. Masson staining showed that knockdown of TGF-beta 1, but not TGF-beta 2 promoted the expression of type I collagen in SCAPs. Immunohistochemical staining showed that TGF-beta 2 knockdown inhibited DSPP expression in SCAPs, but TGF-beta 1 knockdown had no obvious effect on DSPP expression. In vivo, TGF-beta 1 overexpression and TGF-beta 2 overexpression had no effect on the expression of type I collagen and DSPP in BMSCs. Conclusions: TGF-beta 2 promotes odontogenic differentiation of SCAPs and attenuates osteogenic differentiation of SCAPs and BMSCs. TGF-beta 1 promotes osteogenic differentiation of BMSCs and plays a complex role in regulating odontogenic differentiation of MSCs.
引用
收藏
页数:10
相关论文
共 45 条
[1]   Effects of a Bioactive Scaffold Containing a Sustained Transforming Growth Factor-β1 releasing Nanoparticle System on the Migration and Differentiation of Stem Cells from the Apical Papilla [J].
Bellamy, Craig ;
Shrestha, Suja ;
Torneck, Calvin ;
Kishen, Anil .
JOURNAL OF ENDODONTICS, 2016, 42 (09) :1385-1392
[2]   Betaglycan: A multifunctional accessory [J].
Bilandzic, Maree ;
Stenvers, Kaye L. .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2011, 339 (1-2) :180-189
[3]   Pulp-dentin Regeneration: Current State and Future Prospects [J].
Cao, Y. ;
Song, M. ;
Kim, E. ;
Shon, W. ;
Chugal, N. ;
Bogen, G. ;
Lin, L. ;
Kim, R. H. ;
Park, N. -H. ;
Kang, M. K. .
JOURNAL OF DENTAL RESEARCH, 2015, 94 (11) :1544-1551
[4]   Comparative analysis of transforming growth factor-beta isoforms 1-3 in human and rabbit dentine matrices [J].
Cassidy, N ;
Fahey, M ;
Prime, SS ;
Smith, AJ .
ARCHIVES OF ORAL BIOLOGY, 1997, 42 (03) :219-223
[5]   Effects of TGF-βs on the growth, collagen synthesis and collagen lattice contraction of human dental pulp fibroblasts in vitro [J].
Chan, CP ;
Lan, WH ;
Chang, MC ;
Chen, YJ ;
Lan, WC ;
Chang, HH ;
Jeng, JH .
ARCHIVES OF ORAL BIOLOGY, 2005, 50 (05) :469-479
[6]   Role of ALK5/Smad2/3 and MEK1/ERK Signaling in Transforming Growth Factor Beta 1-modulated Growth, Collagen Turnover, and Differentiation of Stem Cells from Apical Papilla of Human Tooth [J].
Chang, Hsiao-Hua ;
Chang, Mei-Chi ;
Wu, I-Hua ;
Huang, Guay-Fen ;
Huang, Wei-Ling ;
Wang, Yin-Lin ;
Lee, Sheng-Yang ;
Yeh, Chien-Yang ;
Guo, Ming-Kuang ;
Chan, Chiu-Po ;
Hsien, Hsiang-Chi ;
Jeng, Jiiang-Huei .
JOURNAL OF ENDODONTICS, 2015, 41 (08) :1272-1280
[7]   Betaglycan drives the mesenchymal stromal cell osteogenic program and prostate cancer-induced osteogenesis [J].
Cook, Leah M. ;
Frieling, Jeremy S. ;
Nerlakanti, Niveditha ;
McGuire, Jeremy J. ;
Stewart, Paul A. ;
Burger, Karen L. ;
Cleveland, John L. ;
Lynch, Conor C. .
ONCOGENE, 2019, 38 (44) :6959-6969
[8]  
DenBesten P K, 2001, Adv Dent Res, V15, P39
[9]   Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype [J].
Erlebacher, A ;
Derynck, R .
JOURNAL OF CELL BIOLOGY, 1996, 132 (1-2) :195-210
[10]   Comparative Evaluation of Chemotactic Factor Effect on Migration and Differentiation of Stem Cells of the Apical Papilla [J].
Fayazi, Sara ;
Takimoto, Koyo ;
Diogenes, Anibal .
JOURNAL OF ENDODONTICS, 2017, 43 (08) :1288-1293