Amelogenin promotes odontoblast-like MDPC-23 cell differentiation via activation of ERK1/2 and p38 MAPK

Yao, Naihui; Li, Shiting; Jiang, Yong; Qiu, Songbo; Tan, Yinghui

doi:10.1007/s11010-011-0842-1

Cited by 10 publications

(9 citation statements)

References 17 publications

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“…The roles of FGFR/MEK/Erk1/2 signaling in odontoblast differentiation and the crosstalk between the FGF/FGFR and BMP/BMPR signaling pathways in the stimulatory effects of FGF2 on odontoblast differentiation in our study are consistent with previously reported roles of these pathways in osteoblasts (Fakhry et al 2005;Spector et al 2005;Ye et al 2006;Yao et al 2011;Marie 2012;Marie et al 2012;Zhang et al 2012;Zhao et al 2012).…”

Section: Discussionsupporting

confidence: 93%

Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2

et al. 2015

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Members of the fibroblast growth factor (FGF) family play essential and important roles in primary and reparative dentinogenesis. Although there appears to be a general agreement on the effects of FGF signaling on the proliferation of pulp cells, there are conflicting results regarding its effects on odontoblast differentiation. We recently examined the effects of continuous exposure of dental pulp cells to FGF2 and showed that the effects of FGF2 on differentiation of progenitor cells into odontoblasts were stage specific and dependent on the stage of cell maturity. The purpose of this study was to gain further insight into cellular and molecular mechanisms regulating the stimulatory effects of FGF2 on odontoblast differentiation. To do so, we examined the effects of early and limited exposure of pulp cells from a series of green fluorescent protein (GFP) reporter transgenic mice that display stage-specific activation of transgenes during odontoblast differentiation to FGF2. Our results showed that early and limited exposure of pulp cells to FGF2 did not have significant effects on the extent of mineralization but induced significant increases in the expression of Dmp1 and Dspp and the number of DMP1-GFP + and DSPP-Cerulean + odontoblasts. Our results also showed that the stimulatory effects of FGF2 on odontoblast differentiation were mediated through FGFR/MEK/Erk1/2 signaling, increases in Bmp2, and activation of the BMP/BMPR signaling pathway. These observations show that early and limited exposure of pulp cells to FGF2 alone promotes odontoblast differentiation and provides critical insight for applications of FGF2 in dentin regeneration.

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Section: Discussionsupporting

confidence: 93%

Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2

et al. 2015

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“…It has been reported that several compounds, such as sodium fluoride (NaF) [27], amelogenin [28], or lipopolysaccharide (LPS) [29], can activate the ERK1/2 signaling pathway in MDPC-23 cells. The activation of the ERK1/2 signaling pathway was found to be crucial for regulating p35 expression [14–16,30], and it has also been reported that TGF-β1 can activate non-Smad signaling pathways such as the ERK1/2 pathway [31].…”

Section: Resultsmentioning

confidence: 99%

TGF-β1 Sensitizes TRPV1 through Cdk5 Signaling in Odontoblast-Like Cells

et al. 2013

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BackgroundOdontoblasts are specialized cells that form dentin and they are believed to be sensors for tooth pain. Transforming growth factor-β1 (TGF-β1), a pro-inflammatory cytokine expressed early in odontoblasts, plays an important role in the immune response during tooth inflammation and infection. TGF-β1 is also known to participate in pain signaling by regulating cyclin-dependent kinase 5 (Cdk5) in nociceptive neurons of the trigeminal and dorsal root ganglia. However, the precise role of TGF-β1 in tooth pain signaling is not well characterized. The aim of our present study was to determine whether or not in odontoblasts Cdk5 is functionally active, if it is regulated by TGF-β1, and if it affects the downstream pain receptor, transient receptor potential vanilloid-1 (TRPV1).ResultsWe first determined that Cdk5 and p35 are indeed expressed in an odontoblast-enriched primary preparation from murine teeth. For the subsequent analysis, we used an odontoblast-like cell line (MDPC-23) and found that Cdk5 is functionally active in these cells and its kinase activity is upregulated during cell differentiation. We found that TGF-β1 treatment potentiated Cdk5 kinase activity in undifferentiated MDPC-23 cells. SB431542, a specific inhibitor of TGF-β1 receptor 1 (Tgfbr1), when co-administered with TGF-β1, blocked the induction of Cdk5 activity. TGF-β1 treatment also activated the ERK1/2 signaling pathway, causing an increase in early growth response-1 (Egr-1), a transcription factor that induces p35 expression. In MDPC-23 cells transfected with TRPV1, Cdk5-mediated phosphorylation of TRPV1 at threonine-407 was significantly increased after TGF-β1 treatment. In contrast, SB431542 co-treatment blocked TRPV1 phosphorylation. Moreover, TGF-β1 treatment enhanced both proton- and capsaicin-induced Ca2+ influx in TRPV1-expressing MDPC-23 cells, while co-treatment with either SB431542 or roscovitine blocked this effect.ConclusionsCdk5 and p35 are expressed in a murine odontoblast-enriched primary preparation of cells from teeth. Cdk5 is also functionally active in odontoblast-like MDPC-23 cells. TGF-β1 sensitizes TRPV1 through Cdk5 signaling in MDPC-23 cells, suggesting the direct involvement of odontoblasts and Cdk5 in dental nociceptive pain transduction.

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“…Enamel matrix derivatives have been studied extensively both in vitro and in vivo. Amelogenin has been shown to stimulate osteoblast differentiation (Olivares-Navarrete et al, 2013) and to increase the mitogen activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK1/2) (Yao et al, 2011), implicating this signaling cascade in its mechanism of action. However, the specific roles of other components of these extracts on cell response are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Role of the N-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells

Olivares-Navarrete

Vesper

Hyzy

et al. 2014

eCM

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Porcine enamel matrix derivative (pEMD), a complex mixture of proteins and peptides including full-length amelogenin protein, splice variants, and proteolytic peptides, is used clinically with a carrier to regenerate supportive tissue around teeth. During application, pEMD self-assembles as nanospheres and precipitates as a three-dimensional matrix to facilitate cell migration and differentiation. Amelogenin, the primary constituent of pEMD, stimulates osteoblast differentiation, but it is unclear what specific roles other components of pEMD play in determining biological response. This study examined the potential of one constituent of pEMD, the N-terminal amelogenin peptide (NTAP), to promote osteoblastic differentiation of human mesenchymal stem cells (MSCs) and to elucidate possible signaling pathways involved. Effects of porcine NTAP on MSC cultures were compared to those of recombinant human amelogenin. While amelogenin induced MSC osteoblastic differentiation, a more robust osteoblastic response was seen after NTAP treatment. A phospho-kinase proteasome array measuring phosphorylation of 35 proteins indicated that protein kinase C (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2), and β-catenin were highly phosphorylated by NTAP. This was confirmed by measuring PKC activity and levels of phospho-ERK1/2 and β-catenin. Both amelogenin and NTAP increased PKC, but NTAP induced higher phosho-ERK1/2 and phospho-β-catenin than amelogenin. ERK1/2 inhibition blocked both amelogeninand NTAP-induced increases in RUNX2, ALP, OCN, COL1, and BMP2. The results demonstrate that NTAP induces osteogenic differentiation of MSCs via PKC and ERK1/2 activation and β-catenin degradation. NTAP may be an active bone regeneration component of amelogenin, and may play this role in pEMD-stimulated periodontal regeneration.

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Amelogenin promotes odontoblast-like MDPC-23 cell differentiation via activation of ERK1/2 and p38 MAPK

Cited by 10 publications

References 17 publications

Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2

Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2

TGF-β1 Sensitizes TRPV1 through Cdk5 Signaling in Odontoblast-Like Cells

Role of the N-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells

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