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BMC Oral Health
Published in: BMC Oral Health 1/2020

Open Access 01-12-2020 | Research article

Effects of ERK/p38 MAPKs signaling pathways on MTA-mediated osteo/odontogenic differentiation of stem cells from apical papilla: a vitro study

Authors: Jing Du, Yating Lu, Mengxiao Song, Lin Yang, Junqing Liu, Xinyu Chen, Yue Ma, Yan Wang

Published in: BMC Oral Health | Issue 1/2020

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Abstract

Background

Stem cells from apical papilla (SCAP) located in the root apex of immature permanent teeth are a reliable cell source for pulp-dentine complex regeneration. Mineral trioxide aggregate (MTA) is a biocompatible material which has been widely used in endodontic treatments. The aim of this study was to elucidate the regulatory role of MTA in the proliferation and differentiation of SCAP.

Methods

Cell viability was detected by Cell counting kit-8. Characteristics of SCAP were confirmed by Flow cytometric (FCM) analysis and alizarin red staining. Then, MTA-mediated osteo/odontogenic differentiation of SCAP was investigated by reverse transcription polymerase chain reaction. The effect of MAPKs on MTA-mediated osteo/odontogenic differentiation was evaluated by western blot analysis.

Results

There was no significant difference in cell viability between the control group and the group with lower concentrations of MTA. However, higher concentrations of MTA could inhibit proliferation of SCAP. It is demonstrated that the ALP activity were enhanced, the mRNA and protein expression of BSP, OCN, DSPP, Runx2 were up-regulated. In addition, phosphorylation proteins of ERK, p38 were activated through western blot analysis.

Conclusions

MTA at appropriate concentration could enhance osteo/odontogenic differentiation of SCAP by activating p38 and ERK signaling pathways. This study provides a new idea for the clinical application of MTA and the treatment of endodontic diseases.
Appendix
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Literature
1.
2.
Chueh LH, Huang GT. Immature teeth with periradicular periodontitis or abscess undergoing apexogenesis: a paradigm shift. J Endod. 2006;32(12):1205–13.PubMedCrossRef
3.
Mastrangelo F, Scacco S, Ballini A, Quaresima R, Gnoni A, De Vito D, Scarano A, Dipalma G, Gargiulo Isacco C, Cantore S, Coscia MF, Pettini F, Sammartino G, Cicciu M, Conti P, Lo ML. A pilot study of human mesenchymal stem cells from visceral and sub-cutaneous fat tissue and their differentiation to osteogenic phenotype. Eur Rev Med Phaemacol Sci. 2019;23:2924–34.
4.
EI Omar R, Beroud J, Stoltz JF, Menu P, Velot E, Decot V. Umbilical cord Mesenchymal stem cells: the new gold standard for Mesenchymal stem cell-based therapies? Tissue Eng Part B Rev. 2014;20(5):523–44.CrossRef
5.
6.
Ballini A, Di Benedetto A, De Vito D, Scarano A, Scacco S, Perillo L, Posa F, Dipalma G, Paduano F, Contaldo M, Grano M, Brunetti G, Colaianni G, Di Cosola M, Cantore S, Mori G. Stemness genes expression in naïve vs. osteodifferentiated human dental-derived stem cells. Eur Rev Med Pharmacol Sci. 2019;23(7):2916–23.PubMed
7.
Ballini A, Cantore S, Scacco S, Perillo L, Scarano A, Aityan SK, Contaldo M, Cd Nguyen K, Santacroce L, Syed J, De Vito D, Dipalma G, Gargiulo Isacco C, Inchingolo F. A comparative study on different stemness gene expression between dental pulp stem cells vs. dental bud stem cells. Eur Rev Med Pharmacol Sci. 2019;23(4):1626–33.PubMed
8.
Cantore S, Crincoli V, Boccaccio A, Uva AE, Fiorentino M, Monno G, Bollero P, Derla C, Fabiano F, Ballini A, Santacroce L. Recent advances in endocrine, metabolic and immune disorders: Mesenchymal stem cells (MSCs) and engineered scaffolds. Endocr Metab Immune Disord Drug Targets. 2018;18(5):466–9.PubMedCrossRef
9.
Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S, Huang GT. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod. 2008;34(2):166–71.PubMedPubMedCentralCrossRef
10.
Bakopoulou A, Leyhausen G, Volk J, Tsiftsoglou A, Garefis P, Koidis P, Geurtsen W. Comparative analysis of in vitro osteo/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP). Arch Oral Biol. 2011;56(7):709–21.PubMedCrossRef
11.
Cantore S, Ballini A, De Vito D, Martelli FS, Georgakopoulos I, Almasri M, Dibello V, Altini V, Farronato G, Dipalma G, Farronato D, Inchingolo F. Characterization of human apical papilla-derived stem cells. J Biol Regul Homeost Agents. 2017;31(4):901–10.PubMed
12.
Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu H, Gronthos S, Wang CY, Wang S, et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One. 2006;1:e79.PubMedPubMedCentralCrossRef
13.
Huang GT, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS, Shi S. Stem/progenitor cell–mediated De novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng Part A. 2010;16(2):605–15.PubMedCrossRef
14.
Di Benedetto A, Posa F, De Maria S, Ravagnan G, Ballini A, Porro C, Trotta T, Grano M, Muzio LL, Mori G. Polydatin, natural precursor of resveratrol, promotes Osteogenic differentiation of Mesenchymal stem cells. Int J Med Sci. 2018;15(9):944–52.PubMedPubMedCentralCrossRef
15.
Zhao XE, Yang Z, Zhang H, Yao G, Liu J, Wei Q, Ma B. Resveratrol promotes Osteogenic differentiation of canine bone marrow Mesenchymal stem cells through Wnt/Beta-catenin signaling pathway. Cell Reprogram. 2018;20(6):371–81.PubMedCrossRef
16.
Cheng Y, Huang L, Wang Y, Huo Q, Shao Y, Bao H, Li Z, Liu Y, Li X. Strontium promotes osteogenic differentiation by activating autophagy via the the AMPK/mTOR signaling pathway in MC3T3-E1 cells. Int J Mol Med. 2019;44(2):652–60.PubMedPubMedCentral
17.
Parirokh M, Torabinejad M. Mineral trioxide aggregate: a comprehensive literature review--part III: clinical applications, drawbacks, and mechanism of action. J Endod. 2010;36(3):400–13.PubMedCrossRef
18.
Roberts HW, Toth JM, Berzins DW, Charlton DG. Mineral trioxide aggregate material use in endodontic treatment: a review of the literature. Dent Mater. 2008;24(2):149–64.PubMedCrossRef
19.
Cheng Y, Huang L, Wang Y, Huo Q, Shao Y, Bao H, Li Z, Liu Y, Li X. Reaction of dogs' teeth to root canal filling with mineral trioxide aggregate or a glass ionomer sealer. Int J Mol Med. 2019;44(2):652–60.PubMedPubMedCentral
20.
Torabinejad M, Parirokh M. Mineral trioxide aggregate: a comprehensive literature review--part II: leakage and biocompatibility investigations. J Endod. 2010;36(2):190–202.PubMedCrossRef
21.
Nair PN, Duncan HF, Pitt Ford TR, Luder HU. Histological, ultrastructural and quantitative investigations on the response of healthy human pulps to experimental capping with mineral trioxide aggregate: a randomized controlled trial. Br Dent J. 2008;205(11):597.
22.
Seo MS, Hwang KG, Lee J, Kim H, Baek SH. The effect of mineral trioxide aggregate on odontogenic differentiation in dental pulp stem cells. J Endod. 2013;39(2):242–8.PubMedCrossRef
23.
Torabinejad M, Hong CU, McDonald F, Pitt Ford TR. Physical and chemical properties of a new root-end filling material. J Endod. 1995;21(7):349–53.PubMedCrossRef
24.
Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002;298(5600):1911–2.PubMedCrossRef
25.
Wang L, Wu F, Song Y, Duan Y, Jin Z. Erythropoietin induces the osteogenesis of periodontal mesenchymal stem cells from healthy and periodontitis sources via activation of the p38 MAPK pathway. Int J Mol Med. 2018;41(2):829–35.PubMed
26.
Cai TY, Zhu W, Chen XS, Zhou SY, Jia LS, Sun YQ. Fibroblast growth factor 2 induces mesenchymal stem cells to differentiate into tenocytes through the MAPK pathway. Mol Med Rep. 2013;8(5):1323–8.PubMedCrossRef
27.
Zhao X, He W, Song Z, Tong Z, Li S, Ni L. Mineral trioxide aggregate promotes odontoblastic differentiation via mitogen-activated protein kinase pathway in human dental pulp stem cells. Mol Biol Rep. 2012;39(1):215–20.PubMedCrossRef
28.
Huang GT, Sonoyama W, Liu Y, Liu H, Wang S, Shi S. The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering. J Endod. 2008;34(6):645–51.PubMedPubMedCentralCrossRef
29.
Hakki SS, Bozkurt SB, Hakki EE, Belli S. Effects of mineral trioxide aggregate on cell survival, gene expression associated with mineralized tissues, and biomineralization of cementoblasts. J Endod. 2009;35(4):513–9.PubMedCrossRef
30.
Qin C, Brunn JC, Cadena E, Ridall A, Butler WT. Dentin sialoprotein in bone and dentin sialophosphoprotein gene expressed by osteoblasts. Connect Tissue Res. 2003;44(Suppl 1):179–83.PubMedCrossRef
31.
Papagerakis P, Berdal A, Mesbah M, Peuchmaur M, Malaval L, Nydegger J, Simmer J, Macdougall M. Investigation of osteocalcin, osteonectin, and dentin sialophosphoprotein in developing human teeth. Bone. 2002;30(2):377–85.PubMedCrossRef
32.
Tsukamoto Y, Fukutani S, Shin-Ike T, Kubota T, Sato S, Suzuki Y, Mori M. Mineralized nodule formation by cultures of human dental pulp-derived fibroblasts. Arch Oral Biol. 1992;37(12):1045–55.PubMedCrossRef
33.
34.
Wu L, Zhu F, Wu Y, Lin Y, Nie X, Jing W, Qiao J, Liu L, Tang W, Zheng X. Dentin sialophosphoprotein-promoted mineralization and expression of odontogenic genes in adipose-derived stromal cells. Cells Tissues Organs. 2008;187(2):103–12.PubMedCrossRef
35.
Khan SZ, Kokubu E, Matsuzaka K, Inoue T. Behaviour of rat-cultured dental pulp cells in three-dimensional collagen type-1 gel in vitro and in vivo. Aust Endod J. 2013;39(3):137–45.PubMedCrossRef
36.
Chen S, Gluhak-Heinrich J, Wang YH, Wu YM, Chuang HH, Chen L, Yuan GH, Dong J, Gay I, MacDougall M. Runx2, Osx, and Dspp in tooth development. J Dent Res. 2009;88:904.PubMedPubMedCentralCrossRef
37.
Neugebauer BM, Moore MA, Broess M, Gerstenfeld LC, Hauschka PV. Characterization of structural sequences in the chicken osteocalcin gene: expression of osteocalcin by maturing osteoblasts and by hypertrophic chondrocytes in vitro. J Bone Miner Res. 1995;10(1):157–163.CrossRef
38.
Ge C, Xiao G, Jiang D, Franceschi RT. Critical role of the extracellular signal–regulated kinase–MAPK pathway in osteoblast differentiation and skeletal development. J Cell Biol. 2007;176(5):709–18.PubMedPubMedCentralCrossRef
39.
Greenblatt MB, Shim JH, Zou W, Sitara D, Schweitzer M, Hu D, Lotinun S, Sano Y, Baron R. The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice. J Clin Invest. 2010;120(7):2457–73.PubMedPubMedCentralCrossRef
40.
Thouverey C, Caverzasio J. Focus on the p38 MAPK signaling pathway in bone development and maintenance. Bonekey Rep. 2015;10(4):711.
Metadata
Title
Effects of ERK/p38 MAPKs signaling pathways on MTA-mediated osteo/odontogenic differentiation of stem cells from apical papilla: a vitro study
Authors
Jing Du
Yating Lu
Mengxiao Song
Lin Yang
Junqing Liu
Xinyu Chen
Yue Ma
Yan Wang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2020
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-020-1016-x

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