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

被引：41

作者：

Chang, Hsiao-Hua ^{[1
,2
]}

Chang, Mei-Chi ^{[3
,4
]}

Wu, I-Hua ^{[1
,2
]}

Huang, Guay-Fen ^{[1
,2
]}

Huang, Wei-Ling ^{[1
,2
]}

Wang, Yin-Lin ^{[1
,2
]}

Lee, Sheng-Yang ^{[5
]}

Yeh, Chien-Yang ^{[1
,2
]}

Guo, Ming-Kuang ^{[1
,2
]}

Chan, Chiu-Po ^{[6
]}

Hsien, Hsiang-Chi ^{[4
]}

Jeng, Jiiang-Huei ^{[1
,2
]}

机构：

[1] Natl Taiwan Univ Hosp, Dept Dent, Taipei, Taiwan

[2] Natl Taiwan Univ, Coll Med, Sch Dent, Lab Dent Pharmacol Toxicol & Mat Biocompatibil, Taipei 10764, Taiwan

[3] Chang Gung Univ Sci & Technol, Biomed Sci Team, Taoyuan, Taiwan

[4] Chang Gung Mem Hosp, Taoyuan, Taiwan

[5] Taipei Med Univ, Sch Dent, Taipei, Taiwan

[6] Chang Gung Mem Hosp, Dept Dent, Taipei 10591, Taiwan

来源：

JOURNAL OF ENDODONTICS | 2015年 / 41卷 / 08期

关键词：

ALK5; alkaline phosphatase; ERK; signal transduction; Smad2; stem cells from apical papilla; transforming growth factor beta; DENTAL-PULP CELLS; TGF-BETA; IN-VITRO; OSTEOBLAST DIFFERENTIATION; EPITHELIAL-CELLS; POTENTIAL ROLE; MESSENGER-RNA; DNA-SYNTHESIS; TGF-BETA-1; EXPRESSION;

D O I：

10.1016/j.joen.2015.03.022

中图分类号：

R78 [口腔科学];

学科分类号：

1003 ;

摘要：

Introduction: Transforming growth factor beta 1 (TGF-beta 1) plays an important role in cell proliferation, matrix formation, and odontogenesis. This study investigated the effects of TGF-beta 1 on stem cells from apical papilla (SCAPs) and its signaling by MEK/ERK and Smad2. Methods: SCAPs were exposed to TGF-beta 1 with/without pretreatment and coincubation by SB431542 (an ALK5/Smad2/3 inhibitor) or U0126 (a MEK/ERK inhibitor). Cell growth was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay or direct counting of viable cells. Collagen content was determined by using the Sircol collagen assay (Biocolor Ltd, Newtownabbey, Northern Ireland). Cell differentiation was evaluated by measuring alkaline phosphatase (ALP) activity. Smad2 and ERK1/2 phosphorylation was analyzed by Western blotting or PathScan phospho-enzyme-linked immunosorbent assay (Cell Signaling Technology Inc, Danvers, MA). Results: TGF-beta 1 stimulated the growth and collagen content of cultured SCAPs. TGF-beta 1 stimulated ERK1/2 and Smad2 phosphorylation within 60 minutes of exposure. Pretreatment by U0126 and SB431542 effectively prevented the TGF-beta 1 induced cell growth and collagen content in SCAPs. TGF-beta 1 stimulated ALP activity at lower concentrations (0.1-1 ng/mL) but down-regulated ALP at higher concentrations (>5 ng/mL). U0126 prevented 0.5 ng/mL TGF-beta 1-induced ALP activity but showed little effect on 10 ng/mL TGF-beta 1-induced decline of ALP in SCAPs. Interestingly, SB431542 attenuated both the stimulatory and inhibitory effects on ALP by TGF-beta 1. Conclusions: TGF-beta 1 may affect the proliferation, collagen turnover, and differentiation of SCAPs via differential activation of ALK5/Smad2 and MEK/ERK signaling. These results highlight the future use of TGF-beta 1 and SCAP for engineering of pulpal regeneration and apexogenesis.

引用

页码：1272 / 1280

页数：9

共 54 条

[21] Transforming growth factor-β1 to the bone [J].

Janssens, K ;

ten Dijke, P ;

Janssens, S ;

Van Hul, W .

ENDOCRINE REVIEWS, 2005, 26 (06) :743-774

[22] Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-β:: implications for carcinogenesis [J].

Javelaud, D ;

Mauviel, A .

ONCOGENE, 2005, 24 (37) :5742-5750

[23] Smad3 differently affects osteoblast differentiation depending upon its differentiation stage [J].

Kaji, H. ;

Naito, J. ;

Sowa, H. ;

Sugimoto, T. ;

Chihara, K. .

HORMONE AND METABOLIC RESEARCH, 2006, 38 (11) :740-745

[24] Transcript profiling of periodontal fibroblasts and osteoblasts [J].

Lallier, TE ;

Spencer, A ;

Fowler, MM .

JOURNAL OF PERIODONTOLOGY, 2005, 76 (07) :1044-1055

[25] Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells [J].

Li, Rui-Dong ;

Deng, Zhong-Liang ;

Hu, Ning ;

Liang, Xi ;

Liu, Bo ;

Luo, Jinyong ;

Chen, Liang ;

Yin, Liangjun ;

Luo, Xiaoji ;

Shui, Wei ;

He, Tong-Chuan ;

Huang, Wei .

BMB REPORTS, 2012, 45 (09) :509-514

[26] Regeneration of the dentine-pulp complex with revitalization/revascularization therapy: challenges and hopes [J].

Lin, L. M. ;

Ricucci, D. ;

Huang, G. T. -J. .

INTERNATIONAL ENDODONTIC JOURNAL, 2014, 47 (08) :713-724

[27] Transforming growth factor β1 down-regulates Runx-2 and alkaline phosphatase activity of human dental pulp cells via ALK5/Smad2/3 signaling [J].

Lin, Po-Shuen ;

Chang, Mei-Chi ;

Chan, Chiu-Po ;

Lee, Sheng-Yang ;

Lee, Jang-Jaer ;

Tsai, Yi-Ling ;

Tseng, Hui-Chun ;

Tai, Tseng-Fang ;

Lin, Hsueh-Jen ;

Jeng, Jiiang-Huei .

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY, 2011, 111 (03) :394-400

[28] CAMP inhibits transforming growth factor-β-stimulated collagen synthesis via inhibition of extracellular signal-regulated kinase 1/2 and Smad signaling in cardiac fibroblasts [J].

Liu, Xiaoqiu ;

Sun, Shu Qiang ;

Hassid, Aviv ;

Ostrom, Rennolds S. .

MOLECULAR PHARMACOLOGY, 2006, 70 (06) :1992-2003

[29]

MacDougall M, 2001, Adv Dent Res, V15, P25

[30] Dexamethasone inhibition of TGFβ-induced cell growth and type II collagen mRNA expression through ERK-integrated AP-1 activity in cultured rat articular chondrocytes [J].

Miyazaki, Y ;

Tsukazaki, T ;

Hirota, Y ;

Yonekura, A ;

Osaki, M ;

Shindo, H ;

Yamashita, S .

OSTEOARTHRITIS AND CARTILAGE, 2000, 8 (05) :378-385

← 1 2 3 4 5 6 →