Decreasing NF-κB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines

Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized tha...

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Veröffentlicht in:PloS one 2015, Vol.10 (1), p.e0113334-e0113334
Hauptverfasser: Hozhabri, Neda S T, Benson, M Douglas, Vu, Michael D, Patel, Rinkesh H, Martinez, Rebecca M, Nakhaie, Fatemeh N, Kim, Harry K W, Varanasi, Venu G
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container_title PloS one
container_volume 10
creator Hozhabri, Neda S T
Benson, M Douglas
Vu, Michael D
Patel, Rinkesh H
Martinez, Rebecca M
Nakhaie, Fatemeh N
Kim, Harry K W
Varanasi, Venu G
description Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor-κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor-κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor-κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor-κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor-κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor-κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor-κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation.
doi_str_mv 10.1371/journal.pone.0113334
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This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor-κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor-κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor-κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor-κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor-κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor-κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor-κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. 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This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor-κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor-κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor-κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor-κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor-κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor-κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor-κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25629155</pmid><doi>10.1371/journal.pone.0113334</doi><oa>free_for_read</oa></addata></record>
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subjects Alkaline phosphatase
Cell differentiation
Cell Differentiation - drug effects
Cell Differentiation - genetics
Cell morphology
Cells, Cultured
Collagen
Collagen - genetics
Collagen - metabolism
Cytokines
Cytokines - pharmacology
Cytology
Dental materials
Dental pulp
Dental Pulp - cytology
Dentin
Dentistry
Differentiation (biology)
Dspp protein
Extracellular matrix
Extracellular Matrix - metabolism
Fibroblasts
Gene Expression
Gene Knockdown Techniques
Humans
Inflammation
Inflammation Mediators - pharmacology
Inflammatory response
Interleukins
Kinases
Leupeptins - pharmacology
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - drug effects
Mesenchymal Stem Cells - metabolism
Nestin
NF-kappa B - genetics
NF-kappa B - metabolism
NF-κB protein
Odontoblasts
Odontoblasts - cytology
Odontoblasts - drug effects
Odontoblasts - metabolism
Rheumatoid arthritis
RNA Interference
RNA, Small Interfering - genetics
Signaling
siRNA
Stem cells
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
Synaptotagmin
Tissue engineering
Tumor necrosis factor-TNF
Tumor necrosis factor-α
title Decreasing NF-κB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines
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