scholarly journals The Reduction of JunB Inhibits the Odontogenic Differentiation Potential of the DPSCs by Targeting PIN1 in Pulpitis

Author(s):  
Lei Li ◽  
Chengfeng Jiang ◽  
Yongchun Gu ◽  
Rongrong Jiang ◽  
Jianpeng Han ◽  
...  

Abstract Pulpitis is an inflammatory condition that can lead to the loss of tooth vitality. The odontogenic differentiation potential of the dental pulp stem cells (DPSCs) is significantly decreased in the pulpitis microenvironment. The aim of this study was to determine the mechanism of the impaired odontogenic differentiation of the DPSCs in an inflammatory microenvironment. Overexpression and inhibition of the JunB were performed to evaluate its effect on the odontogenic differentiation potential of the DPSCs. The results showed that the JunB was positively correlated with the odontogenic differentiation ability of the DPSCs. The co-immunoprecipitation assay coupled with the mass spectrometry showed that peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1 (PIN1) was a downstream target of the JunB. Moreover, the expression of PIN1 was negatively correlated with the odontogenic differentiation potential of the DPSCs. Taken together, the decreased expression level of the JunB in an inflammatory state can impair the odontogenic differentiation ability of the DPSCs by upregulating the expression of the PIN1, a negative regulator of the odontogenic differentiation of the DPSCs.

Author(s):  
Seung Chung ◽  
William Cheng ◽  
Yessenia Valverde ◽  
Nam-Seob Lee ◽  
Hassan Marzban ◽  
...  

The multipotent nature of dental pulp stem cells (DPSCs) promises regenerative endodontic potentials. Alterations in microenvironment have been shown to control the differentiation phenotypes of DPSCs. Understanding the biological mechanisms and finding the optimal DPSC differentiation protocols are crucial for successful DPSC engineering strategies in pulp and dentin healing. The aim of this study is to identify the role of p38 mitogen-activated protein kinase (p38) under normal and oxygen-deprived conditions (2%) to reveal its effect on odontogenic DPSC differentiation. Human DPSCs were isolated from healthy molars and underwent odontogenic differentiation in regular and osteogenic media treated with SB203580, a p38 inhibitor, for 72 hours, and then swapped with osteogenic media for 21 days under hypoxic condition. Immunochemistry and PCR analysis for the various odontogenic differentiation genes and proteins were performed. Our PCR data demonstrate that p38 inhibition resulted in a significant upregulation in odontogenic gene expressions such as DMP-1, DSPP, RUNX, and OSX in normal conditions. Under hypoxia, this effect was reversed. These results were further supported by DSPP immunohistochemistry. The DSPP expression under hypoxia was significantly weaker compared to the control. Our results indicate that p38 represents a negative regulator of the odontogenic DPSC differentiation in normoxia. Under hypoxia, p38 exerts a positive function of DPSC differentiation. Taken together, we identified the p38 and oxygen level as crucial factors to control odontogenic DPSC differentiation providing their essential roles in designing for successful pulp-dentin complex engineering strategies.


2016 ◽  
Vol 42 (4) ◽  
pp. 575-583 ◽  
Author(s):  
Boon Chin Heng ◽  
Xin Ye ◽  
Yuan Liu ◽  
Waruna Lakmal Dissanayaka ◽  
Gary Shun Pan Cheung ◽  
...  

2017 ◽  
Vol 21 (9) ◽  
pp. 2827-2839 ◽  
Author(s):  
Diana Gabriela Soares ◽  
Hebert Luís Rosseto ◽  
Débora Salles Scheffel ◽  
Fernanda Gonçalves Basso ◽  
Claudia Huck ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jiangyi Wang ◽  
Guoqing Li ◽  
Lei Hu ◽  
Fei Yan ◽  
Bin Zhao ◽  
...  

Retinoic acid (RA) signal is involved in tooth development and osteogenic differentiation of mesenchymal stem cells (MSCs). Dental pulp stem cells (DPSCs) are one of the useful MSCs in tissue regeneration. However, the function of RA in osteo/odontogenic differentiation of DPSCs remains unclear. Here, we investigated the expression pattern of RA in miniature pig tooth germ and intervened in the RA signal during osteo/odontogenic differentiation of human DPSCs. Deciduous canine (DC) germs of miniature pigs were observed morphologically, and the expression patterns of RA were studied by in situ hybridization (ISH). Human DPSCs were isolated and cultured in osteogenic induction medium with or without RA or BMS 493, an inverse agonist of the pan-retinoic acid receptors (pan-RARs). Alkaline phosphatase (ALP) activity assays, alizarin red staining, quantitative calcium analysis, CCK8 assay, osteogenesis-related gene expression, and in vivo transplantation were conducted to determine the osteo/odontogenic differentiation potential and proliferation potential of DPSCs. We found that the expression of RARβ and CRABP2 decreased during crown calcification of DCs of miniature pigs. Activation of RA signal in vitro inhibited ALP activities and mineralization of human DPSCs and decreased the mRNA expression of ALP, osteocalcin, osteopontin, and a transcription factor, osterix. With BMS 493 treatment, the results were opposite. Interference in RA signal decreased the proliferation of DPSCs. In vivo transplantation experiments suggested that osteo/odontogenic differentiation potential of DPSCs was enhanced by inversing RA signal. Our results demonstrated that downregulation of RA signal promoted osteo/odontogenic differentiation of DPSCs and indicated a potential target pathway to improve tissue regeneration.


Author(s):  
Zilong Deng ◽  
Wenjuan Yan ◽  
Xingzhu Dai ◽  
Ming Chen ◽  
Qian Qu ◽  
...  

Dental pulp stem cell (DPSC) transplantation has shown new prospects in dental pulp regeneration, and is of great significance in the treatment of pulpitis and pulp necrosis. The fate and regenerative potential of stem cells are dependent, to a great extent, on their microenvironment, which is composed of various tissue components, cell populations, and soluble factors. N-cadherin-mediated cell–cell interaction has been implicated as an important factor in controlling the cell-fate commitment of mesenchymal stem cells. In this study, the effect of N-cadherin on odontogenic differentiation of DPSCs and the potential underlying mechanisms, both in vitro and in vivo, was investigated using a cell culture model and a subcutaneous transplantation mouse model. It was found that the expression of N-cadherin was reversely related to the expression of odontogenic markers (dentin sialophosphoprotein, DSPP, and runt-related transcription factor 2, Runx2) during the differentiation process of DPSCs. Specific shRNA-mediated knockdown of N-cadherin expression in DPSCs significantly increased the expression of DSPP and Runx2, alkaline phosphatase (ALP) activity, and the formation of mineralized nodules. Notably, N-cadherin silencing promoted nucleus translocation and accumulation of β-catenin. Inhibition of β-catenin by a specific inhibitor XAV939, reversed the facilitating effects of N-cadherin downregulation on odontogenic differentiation of DPSCs. In addition, knockdown of N-cadherin promoted the formation of odontoblast-like cells and collagenous matrix in β-tricalcium phosphate/DPSCs composites transplanted into mice. In conclusion, N-cadherin acted as a negative regulator via regulating β-catenin activity during odontogenic differentiation of DPSCs. These data may help to guide DPSC behavior by tuning the N-cadherin-mediated cell–cell interactions, with implications for pulp regeneration.


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