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Cell and Tissue Research

, Volume 356, Issue 1, pp 171–182 | Cite as

Dentin matrix proteins (DMPs) enhance differentiation of BMMSCs via ERK and P38 MAPK pathways

  • Yan Yu
  • Lijuan Wang
  • Jinhua Yu
  • Gang Lei
  • Ming Yan
  • Gay Smith
  • Paul R. Cooper
  • Chunbo Tang
  • Guangdong ZhangEmail author
  • Anthony J. SmithEmail author
Regular Article

Abstract

Dentin, the predominant mineralized tissue of the tooth, comprises an extracellular matrix of collagen and a heterogeneous mixture of non-collagenous components, many of which have cellular signaling properties. These properties may be important in signaling stem cell involvement in tissue regeneration following injury and the present study investigates their morphogenic effects on differentiation of Bone Marrow Stromal Stem Cells (BMMSCs) in vitro. Non-collagenous dentin matrix proteins (DMPs) were isolated from healthy human teeth and their effects on BMMSCs behavior examined during in vitro culture. In vitro, DMPs enhanced alkaline phosphatase activity and mineralization in BMMSCs cultures as well as increasing the expression of dentinogenic and osteogenic differentiation markers (including runt-related transcription factor 2, osterix, bone sialoprotein, dentin sialophosphoprotein and osteocalcin) at both transcript and protein levels, with 10 μg/mL DMPs being the optimal stimulatory concentration. Expression of phosphor-ERK/phosphor-P38 in BMMSCs was up-regulated by DMPs and, in the presence of the ERK1/2- and p38-specific inhibitors, the differentiation of BMMSCs was inhibited. These data indicate that DMPs promote the dentinogenic/osteogenic differentiation of BMMSCs via the ERK/p38 MAPK pathways.

Keywords

Dentin matrix proteins Dentinogenesis Osteogenesis Bone marrow-derived mesenchymal stem cells 

Abbreviations

AGS

Absorbable gelatin sponges

ALP

Alkaline phosphatase

BMMSCs

Bone marrow-derived mesenchymal stem cells

BSP

Bone sialoprotein

CPC

Cetyl pyridinium chloride

DMP1

Dentin matrix protein 1

DMPs

Dentin matrix proteins

DPP

Dentin phosphoprotein

DPSCs

Dental pulp stem cells

DSP

Dentin sialoprotein

DSPP

Dentin sialophosphoprotein

EMD

Enamel matrix derivative

EMSC

Ectomesenchymal stem cell

ERK

Extracellular regulated protein kinases

FBS

Fetal bovine serum

FCM

Flow cytometry

FGFs

Fibroblast growth factors

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

GFs

Growth factors

JNK

c-Jun N-terminal kinase

MAPK

Mitogen-activated protein kinase

α-MEM

α-minimum essential medium

MTT

3-[4, 5-dimethylthyazol-2-yl] 2, 5-diphenyl tetrazolium bromide

OCN

Osteocalcin

OSX

Osterix

PBS

Phosphate-buffered saline

PDT

Population doubling time

PVDF

Polyvinylidene difluoride

RUNX2

Runt-related transcription factor 2

SD

Sprague–Dawley

TGFs

Transforming growth factors

Notes

Acknowledgments

This work was supported by the “355” Project of Stomatological Hospital of Jiangsu Province (No. 52008202), Nature Science Foundation of Jiangsu Province (No. BK2009346) and Science and Technology Development Fundation of Nanjing Medical University (2012NJMU102). This project was also funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Yan Yu
    • 1
    • 2
  • Lijuan Wang
    • 1
    • 2
  • Jinhua Yu
    • 1
    • 2
  • Gang Lei
    • 1
    • 2
  • Ming Yan
    • 1
    • 2
  • Gay Smith
    • 3
  • Paul R. Cooper
    • 3
  • Chunbo Tang
    • 1
    • 4
  • Guangdong Zhang
    • 1
    • 2
    Email author
  • Anthony J. Smith
    • 3
    Email author
  1. 1.Institute of StomatologyNanjing Medical UniversityNanjingChina
  2. 2.Department of Conservative Dentistry & Endodontics, School of StomatologyNanjing Medical UniversityNanjingPeople’s Republic of China
  3. 3.Oral Biology, School of DentistryUniversity of BirminghamBirminghamUK
  4. 4.Department of Prosthetic Dentistry, School of StomatologyNanjing Medical UniversityNanjingChina

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