DPP promotes odontogenic differentiation of DPSCs through NF-κB signaling

Abstract Dentin phosphophoryn synthesized and processed predominantly by the odontoblasts, functions as both structural and signaling protein. Mechanistic studies revealed that DPP stimulation of DPSCs positively impacted the differentiation of DPSCs into functional odontoblasts. Results show that N...

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Autores principales:	Yinghua Chen, Adrienn Pethö, Amudha Ganapathy, Anne George
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b58dab702c034818a3ce3d753545caf1
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spelling	oai:doaj.org-article:b58dab702c034818a3ce3d753545caf12021-11-14T12:17:16ZDPP promotes odontogenic differentiation of DPSCs through NF-κB signaling10.1038/s41598-021-01359-32045-2322https://doaj.org/article/b58dab702c034818a3ce3d753545caf12021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01359-3https://doaj.org/toc/2045-2322Abstract Dentin phosphophoryn synthesized and processed predominantly by the odontoblasts, functions as both structural and signaling protein. Mechanistic studies revealed that DPP stimulation of DPSCs positively impacted the differentiation of DPSCs into functional odontoblasts. Results show that NF-κB signaling and transcriptional activation of genes involved in odontoblast differentiation were influenced by DPP signaling. Specifically, RelA/p65 subunit of NF-κB was identified as being responsible for the initiation of the differentiation cascade. Confocal imaging demonstrated the nuclear translocation of p65 with DPP stimulation. Moreover, direct binding of nuclear NF-κB p65 subunit to the promoter elements of Runx2, Osx, OCN, MMP1, MMP3, BMP4 and PTX3 were identified by ChIP analysis. Pharmacological inhibition of the NF-κB pathway using TPCA-1, a selective inhibitor of IKK-2 and JSH-23, an inhibitor that prevents nuclear translocation and DNA binding of p65 showed impairment in the differentiation process. Functional studies using Alizarin-Red staining showed robust mineral deposits with DPP stimulation and sparse deposition with defective odontoblast differentiation in the presence of inhibitors. In vivo expression of NF-κB targets such as OSX, OCN, PTX3 and p65 in odontoblasts and dental pulp cells from DSPP null mouse was lower when compared with the wild-type. Overall, the results suggest an important role for DPP-mediated NF-κB activation in the transcriptional regulation of early odontogenic markers that promote differentiation of DPSCs.Yinghua ChenAdrienn PethöAmudha GanapathyAnne GeorgeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yinghua Chen Adrienn Pethö Amudha Ganapathy Anne George DPP promotes odontogenic differentiation of DPSCs through NF-κB signaling
description	Abstract Dentin phosphophoryn synthesized and processed predominantly by the odontoblasts, functions as both structural and signaling protein. Mechanistic studies revealed that DPP stimulation of DPSCs positively impacted the differentiation of DPSCs into functional odontoblasts. Results show that NF-κB signaling and transcriptional activation of genes involved in odontoblast differentiation were influenced by DPP signaling. Specifically, RelA/p65 subunit of NF-κB was identified as being responsible for the initiation of the differentiation cascade. Confocal imaging demonstrated the nuclear translocation of p65 with DPP stimulation. Moreover, direct binding of nuclear NF-κB p65 subunit to the promoter elements of Runx2, Osx, OCN, MMP1, MMP3, BMP4 and PTX3 were identified by ChIP analysis. Pharmacological inhibition of the NF-κB pathway using TPCA-1, a selective inhibitor of IKK-2 and JSH-23, an inhibitor that prevents nuclear translocation and DNA binding of p65 showed impairment in the differentiation process. Functional studies using Alizarin-Red staining showed robust mineral deposits with DPP stimulation and sparse deposition with defective odontoblast differentiation in the presence of inhibitors. In vivo expression of NF-κB targets such as OSX, OCN, PTX3 and p65 in odontoblasts and dental pulp cells from DSPP null mouse was lower when compared with the wild-type. Overall, the results suggest an important role for DPP-mediated NF-κB activation in the transcriptional regulation of early odontogenic markers that promote differentiation of DPSCs.
format	article
author	Yinghua Chen Adrienn Pethö Amudha Ganapathy Anne George
author_facet	Yinghua Chen Adrienn Pethö Amudha Ganapathy Anne George
author_sort	Yinghua Chen
title	DPP promotes odontogenic differentiation of DPSCs through NF-κB signaling
title_short	DPP promotes odontogenic differentiation of DPSCs through NF-κB signaling
title_full	DPP promotes odontogenic differentiation of DPSCs through NF-κB signaling
title_fullStr	DPP promotes odontogenic differentiation of DPSCs through NF-κB signaling
title_full_unstemmed	DPP promotes odontogenic differentiation of DPSCs through NF-κB signaling
title_sort	dpp promotes odontogenic differentiation of dpscs through nf-κb signaling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b58dab702c034818a3ce3d753545caf1
work_keys_str_mv	AT yinghuachen dpppromotesodontogenicdifferentiationofdpscsthroughnfkbsignaling AT adriennpetho dpppromotesodontogenicdifferentiationofdpscsthroughnfkbsignaling AT amudhaganapathy dpppromotesodontogenicdifferentiationofdpscsthroughnfkbsignaling AT annegeorge dpppromotesodontogenicdifferentiationofdpscsthroughnfkbsignaling
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DPP promotes odontogenic differentiation of DPSCs through NF-κB signaling

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