Differential effects of p38 and Erk1/2 on the chondrogenic and osteogenic differentiation of dental pulp stem cells

Ba,Pengfei; Duan,Xiaoyu; Fu,Guo; Lv,Shuyan; Yang,Pishan; Sun,Qinfeng

doi:10.3892/mmr.2017.6563

Differential effects of p38 and Erk1/2 on the chondrogenic and osteogenic differentiation of dental pulp stem cells

Authors:
- Pengfei Ba
- Xiaoyu Duan
- Guo Fu
- Shuyan Lv
- Pishan Yang
- Qinfeng Sun
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Affiliations: Department of Periodontology, School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China, National Engineering Laboratory, WeGo Group Co., Ltd., Weihai, Shandong 264210, P.R. China, Department of Periodontology, Weihai Stomatological Hospital, Weihai, Shandong 264200, P.R. China
Published online on: May 10, 2017 https://doi.org/10.3892/mmr.2017.6563
Pages: 63-68
Copyright: © Ba et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The extracellular signal-regulated protein kinase 1/2 (Erk1/2) and p38 mitogen‑activated protein‑kinase pathways serve important roles in the regulation of osteogenic and chondrogenic differentiation in mesenchymal stem cells (MSCs). However, the exact mechanism remains unclear, and the effect is controversial. In the present study, the effects of Erk1/2 and p38 on the osteogenic and chondrogenic differentiation of dental pulp stem cells (DPSCs) were compared in vitro. The results indicated that inhibition of Erk1/2 is able to enhance the osteogenic differentiation of DPSCs and inhibit chondrogenic differentiation, whereas inhibition of p38 demonstrated the opposite effect. When compared with previous studies, the present study further confirmed that Erk1/2 and p38 serve important, but complicated, roles in regulating the differentiation of MSCs. Different chemical and physical stimuli, cell types, culture methods, times of inhibitor administration and the dosage of the inhibitor may influence the effect of Erk1/2 and p38 on the differentiation of MSCs. The present study aims to better understand the mechanisms that control the differentiation of MSCs and may be helpful in creating more effective tissue regeneration.

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1	Gehart H, Kumpf S, Ittner A and Ricci R: MAPK signalling in cellular metabolism: Stress or wellness? EMBO Rep. 11:834–840. 2010. View Article : Google Scholar : PubMed/NCBI
2	Garrington TP and Johnson GL: Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol. 11:211–218. 1999. View Article : Google Scholar : PubMed/NCBI
3	Peter AT and Dhanasekaran N: Apoptosis of granulosa cells: A review on the role of MAPK-signalling modules. Reprod Domest Anim. 38:209–213. 2003. View Article : Google Scholar : PubMed/NCBI
4	Stanton LA, Underhill TM and Beier F: MAP kinases in chondrocyte differentiation. Dev Biol. 263:165–175. 2003. View Article : Google Scholar : PubMed/NCBI
5	Stanton LA and Beier F: Inhibition of p38 MAPK signaling in chondrocyte cultures results in enhanced osteogenic differentiation of perichondral cells. Exp Cell Res. 313:146–155. 2007. View Article : Google Scholar : PubMed/NCBI
6	Li C, Yang X, He Y, Ye G, Li X, Zhang X, Zhou L and Deng F: Bone morphogenetic protein-9 induces osteogenic differentiation of rat dental follicle stem cells in P38 and ERK1/2 MAPK dependent manner. Int J Med Sci. 9:862–871. 2012. View Article : Google Scholar : PubMed/NCBI
7	Li L, Han M, Li S, Wang L and Xu Y: Cyclic tensile stress during physiological occlusal force enhances osteogenic differentiation of human periodontal ligament cells via ERK1/2-Elk1 MAPK pathway. DNA Cell Biol. 32:488–497. 2013. View Article : Google Scholar : PubMed/NCBI
8	Pelaez D, Arita N and Cheung HS: Extracellular signal-regulated kinase (ERK) dictates osteogenic and/or chondrogenic lineage commitment of mesenchymal stem cells under dynamic compression. Biochem Biophys Res Commun. 417:1286–1291. 2012. View Article : Google Scholar : PubMed/NCBI
9	Li J, Zhao Z, Liu J, Huang N, Long D, Wang J, Li X and Liu Y: MEK/ERK and p38 MAPK regulate chondrogenesis of rat bone marrow mesenchymal stem cells through delicate interaction with TGF-beta1/Smads pathway. Cell Prolif. 43:333–343. 2010. View Article : Google Scholar : PubMed/NCBI
10	Kim HJ and Im GI: The effects of ERK1/2 inhibitor on the chondrogenesis of bone marrow- and adipose tissue-derived multipotent mesenchymal stromal cells. Tissue Eng Part A. 16:851–860. 2010. View Article : Google Scholar : PubMed/NCBI
11	Bobick BE, Matsche AI, Chen FH and Tuan RS: The ERK5 and ERK1/2 signaling pathways play opposing regulatory roles during chondrogenesis of adult human bone marrow-derived multipotent progenitor cells. J Cell Physiol. 224:178–186. 2010.PubMed/NCBI
12	Zhang W, Walboomers XF, Van Kuppevelt TH, Daamen WF, Van Damme PA, Bian Z and Jansen JA: In vivo evaluation of human dental pulp stem cells differentiated towards multiple lineages. J Tissue Eng Regen Med. 2:117–125. 2008. View Article : Google Scholar : PubMed/NCBI
13	Grottkau BE, Purudappa PP and Lin YF: Multilineage differentiation of dental pulp stem cells from green fluorescent protein transgenic mice. Int J Oral Sci. 2:21–27. 2010. View Article : Google Scholar : PubMed/NCBI
14	Wang FM, Hu T and Zhou X: p38 mitogen-activated protein kinase and alkaline phosphatase in human dental pulp cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 102:114–118. 2006. View Article : Google Scholar : PubMed/NCBI
15	Zhang H, Liu S, Zhou Y, Tan J, Che H, Ning F, Zhang X, Xun W, Huo N, Tang L, et al: Natural mineralized scaffolds promote the dentinogenic potential of dental pulp stem cells via the mitogen-activated protein kinase signaling pathway. Tissue Eng Part A. 18:677–691. 2012. View Article : Google Scholar : PubMed/NCBI
16	Dai J, Wang J, Lu J, Zou D, Sun H, Dong Y, Yu H, Zhang L, Yang T, Zhang X, et al: The effect of co-culturing costal chondrocytes and dental pulp stem cells combined with exogenous FGF9 protein on chondrogenesis and ossification in engineered cartilage. Biomaterials. 33:7699–7711. 2012. View Article : Google Scholar : PubMed/NCBI
17	Gronthos S, Mankani M, Brahim J, Robey PG and Shi S: Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA. 97:13625–13630. 2000. View Article : Google Scholar : PubMed/NCBI
18	Johnstone B, Hering TM, Caplan AI, Goldberg VM and Yoo JU: In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 238:265–272. 1998. View Article : Google Scholar : PubMed/NCBI
19	Dai J, Kuang Y, Fang B, Gong H, Lu S, Mou Z, Sun H, Dong Y, Lu J, Zhang W, et al: The effect of overexpression of Dlx2 on the migration, proliferation and osteogenic differentiation of cranial neural crest stem cells. Biomaterials. 34:1898–1910. 2013. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Wang Y, Li J, Wang Y, Lei L, Jiang C, An S, Zhan Y, Cheng Q, Zhao Z, Wang J and Jiang L: Effects of hypoxia on osteogenic differentiation of rat bone marrow mesenchymal stem cells. Mol Cell Biochem. 362:25–33. 2012. View Article : Google Scholar : PubMed/NCBI
22	Wu Y, Yang Y, Yang P, Gu Y, Zhao Z, Tan L, Zhao L, Tang T and Li Y: The osteogenic differentiation of PDLSCs is mediated through MEK/ERK and p38 MAPK signalling under hypoxia. Arch Oral Biol. 58:1357–1368. 2013. View Article : Google Scholar : PubMed/NCBI
23	Zhang P, Wu Y, Dai Q, Fang B and Jiang L: p38-MAPK signaling pathway is not involved in osteogenic differentiation during early response of mesenchymal stem cells to continuous mechanical strain. Mol Cell Biochem. 378:19–28. 2013. View Article : Google Scholar : PubMed/NCBI
24	Yi C, Liu D, Fong CC, Zhang J and Yang M: Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. ACS Nano. 4:6439–6448. 2010. View Article : Google Scholar : PubMed/NCBI