Mineral trioxide aggregate promotes odontoblastic differentiation via mitogen-activated protein kinase pathway in human dental pulp stem cells

Zhao, Xuyao; Wang, He; Song, Zhenyuan; Tong, Zhongchun; Li, Shiting; Ni, Longxing

doi:10.1007/s11033-011-0728-z

Cited by 105 publications

(113 citation statements)

References 27 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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“…Additionally, TNF-α treatment activates the p38 pathway in dental pulp cells via phosphorylation of p38 and inhibition of p38 diminishes the expression of DPP and DSP38. MTA can induce odontoblastic differentiation of human DPSCs via activation of MAPK signaling42. In a previous study, we demonstrated that LPS can promote the odontoblastic differentiation of human DPSCs via MAPK signaling pathway19.…”

Section: Discussionmentioning

confidence: 85%

IFN-γ regulates human dental pulp stem cells behavior via NF-κB and MAPK signaling

Jiang

Luo

et al. 2017

Sci Rep

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During caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-γ) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-γ at relative high concentration (100 ng/mL) treatment improved the impaired dentinogenic and immunosuppressive regulatory functions of disease-derived dental pulp stem cells (DPSCs). However, little is known about the regulatory effects of IFN-γ at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation). Here we demonstrate that IFN-γ at relatively low concentrations (0.5 ng/mL) promoted the proliferation and migration of DPSCs, but abrogated odonto/osteogenic differentiation. Additionally, we identified that NF-κB and MAPK signaling pathways are both involved in the process of IFN-γ-regulated odonto/osteogenic differentiation of DPSCs. DPSCs treated with IFN-γ and supplemented with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) or SB203580 (a MAPK inhibitor) showed significantly improved potential for odonto/osteogenic differentiation of DPSCs both in vivo and in vitro. These data provide important insight into the regulatory effects of IFN-γ on the biological behavior of DPSCs and indicate a promising therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.

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“…MAPK pathway, which is a non-classical pathway, plays a crucial role in cell growth, proliferation, differentiation and apoptosis. It mainly consists of three parallel mechanisms, i.e., extracellular signal regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs) and p38 MAPK43. The three parallel pathways play crucial roles in regulating the odonto/osteogenic differentiation of many cell types, such as DPSCs, PDLSCs, SCAPs and MSCs893844.…”

Section: Discussionmentioning

confidence: 99%

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

Ma¹,

Liu

Lin

et al. 2016

Sci Rep

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Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation while hsa-let-7c actively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R and hsa-let-7c on the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 and hsa-let-7c over/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated. Alizarin red staining showed that hsa-let-7c low-expression can significantly promote the mineralization of IGF-1 treated SCAPs, while hsa-let-7c over-expression can decrease the calcium deposition of IGF-1 treated SCAPs. Western blot assay and real-time reverse transcription polymerase chain reaction further demonstrated that the expression of odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, COL-I/COL-I, DSPP/DSP, and DMP-1/DMP-1) in IGF-1 treated SCAPs were significantly upregulated in Let-7c-low group. On the contrary, hsa-let-7c over-expression could downregulate the expression of these odonto/osteogenic markers. Moreover, western blot assay showed that the JNK and p38 MAPK signaling pathways were activated in Let-7c-low SCAPs but inhibited in Let-7c-over SCAPs. Together, the IGF-1/IGF-1R/hsa-let-7c axis can control the odonto/osteogenic differentiation of IGF-1-treated SCAPs via the regulation of JNK and p38 MAPK signaling pathways.

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Mineral trioxide aggregate promotes odontoblastic differentiation via mitogen-activated protein kinase pathway in human dental pulp stem cells

Cited by 105 publications

References 27 publications

Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2

Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2

IFN-γ regulates human dental pulp stem cells behavior via NF-κB and MAPK signaling

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

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