Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling

Treated dentin matrix (TDM) is an ideal scaffold material containing multiple extracellular matrix factors. The canonical Wnt signaling pathway is necessary for tooth regeneration. Thus, this study investigated whether the TDM can promote the odontogenic differentiation of human dental pulp stem cel...

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Main Authors: Sirui Liu, Jingjing Sun, Shuai Yuan, Yanyu Yang, Yuping Gong, Ying Wang, Runying Guo, Xue Zhang, Yiming Liu, Hongyan Mi, Meiyue Wang, Mengzhe Liu, Rui Li
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-01-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X21002474
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author Sirui Liu
Jingjing Sun
Shuai Yuan
Yanyu Yang
Yuping Gong
Ying Wang
Runying Guo
Xue Zhang
Yiming Liu
Hongyan Mi
Meiyue Wang
Mengzhe Liu
Rui Li
author_facet Sirui Liu
Jingjing Sun
Shuai Yuan
Yanyu Yang
Yuping Gong
Ying Wang
Runying Guo
Xue Zhang
Yiming Liu
Hongyan Mi
Meiyue Wang
Mengzhe Liu
Rui Li
author_sort Sirui Liu
collection DOAJ
description Treated dentin matrix (TDM) is an ideal scaffold material containing multiple extracellular matrix factors. The canonical Wnt signaling pathway is necessary for tooth regeneration. Thus, this study investigated whether the TDM can promote the odontogenic differentiation of human dental pulp stem cells (hDPSCs) and determined the potential role of Wnt/β-catenin signaling in this process. Different concentrations of TDM promoted the dental differentiation of the hDPSCs and meanwhile, the expression of GSK3β was decreased. Of note, the expression of the Wnt/β-catenin pathway-related genes changed significantly in the context of TDM induction, as per RNA sequencing (RNA seq) data. In addition, the experiment showed that new dentin was visible in rat mandible cultured with TDM, and the thickness was significantly thicker than that of the control group. In addition, immunohistochemical staining showed lower GSK3β expression in new dentin. Consistently, the GSK3β knockdown hDPSCs performed enhanced odotogenesis compared with the control groups. However, GSK3β overexpressing could decrease odotogenesis of TDM-induced hDPSCs. These results were confirmed in immunodeficient mice and Wistar rats. These suggest that TDM promotes odontogenic differentiation of hDPSCs by directly targeting GSK3β and activating the canonical Wnt/β-catenin signaling pathway and provide a theoretical basis for tooth regeneration engineering.
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spelling doaj.art-278270b37b3e4fa89d92696ac77baa232024-04-17T04:17:15ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-01-0178597Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signalingSirui Liu0Jingjing Sun1Shuai Yuan2Yanyu Yang3Yuping Gong4Ying Wang5Runying Guo6Xue Zhang7Yiming Liu8Hongyan Mi9Meiyue Wang10Mengzhe Liu11Rui Li12Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Academy of Medical Sciences at Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaCollege of Materials Science and Engineering, Zhengzhou University Zhengzhou, Henan 450001, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Academy of Medical Sciences at Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Corresponding author.Treated dentin matrix (TDM) is an ideal scaffold material containing multiple extracellular matrix factors. The canonical Wnt signaling pathway is necessary for tooth regeneration. Thus, this study investigated whether the TDM can promote the odontogenic differentiation of human dental pulp stem cells (hDPSCs) and determined the potential role of Wnt/β-catenin signaling in this process. Different concentrations of TDM promoted the dental differentiation of the hDPSCs and meanwhile, the expression of GSK3β was decreased. Of note, the expression of the Wnt/β-catenin pathway-related genes changed significantly in the context of TDM induction, as per RNA sequencing (RNA seq) data. In addition, the experiment showed that new dentin was visible in rat mandible cultured with TDM, and the thickness was significantly thicker than that of the control group. In addition, immunohistochemical staining showed lower GSK3β expression in new dentin. Consistently, the GSK3β knockdown hDPSCs performed enhanced odotogenesis compared with the control groups. However, GSK3β overexpressing could decrease odotogenesis of TDM-induced hDPSCs. These results were confirmed in immunodeficient mice and Wistar rats. These suggest that TDM promotes odontogenic differentiation of hDPSCs by directly targeting GSK3β and activating the canonical Wnt/β-catenin signaling pathway and provide a theoretical basis for tooth regeneration engineering.http://www.sciencedirect.com/science/article/pii/S2452199X21002474Dental pulp stem cellsTreated dentin matrixGSK3βOdontogenic differentiationWnt/β-catenin signaling pathway
spellingShingle Sirui Liu
Jingjing Sun
Shuai Yuan
Yanyu Yang
Yuping Gong
Ying Wang
Runying Guo
Xue Zhang
Yiming Liu
Hongyan Mi
Meiyue Wang
Mengzhe Liu
Rui Li
Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling
Bioactive Materials
Dental pulp stem cells
Treated dentin matrix
GSK3β
Odontogenic differentiation
Wnt/β-catenin signaling pathway
title Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling
title_full Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling
title_fullStr Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling
title_full_unstemmed Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling
title_short Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling
title_sort treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of wnt β catenin signaling
topic Dental pulp stem cells
Treated dentin matrix
GSK3β
Odontogenic differentiation
Wnt/β-catenin signaling pathway
url http://www.sciencedirect.com/science/article/pii/S2452199X21002474
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