scholarly journals Mechanical Stress Stimulates the Osteo/Odontoblastic Differentiation of Human Stem Cells from Apical Papilla via ERK 1/2 and JNK MAPK Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Mu ◽  
Taohong Lv ◽  
Zilu Wang ◽  
Shu Ma ◽  
Jie Ma ◽  
...  

Background Information. Stem cells from apical papilla (SCAPs) are a potent candidate for the apexogenesis/apexification due to their multiple differentiation capacity. During the orthodontic treatment of developing teeth, SCAPsin vivoare usually subjected to the cyclic stress induced by compression forces. However, it remains unclear whether mechanical stress can affect the proliferation and differentiation of human SCAPs.Results. Human SCAPs were isolated and stimulated by 200 g mechanical stimuli for 30 min and their proliferation and differentiation capacity were evaluatedin vitroat different time points. MTT and FCM results demonstrated that cell proliferation was enhanced, while TEM findings showed the morphological and ultrastructural changes in stress-treated SCAPs. ALP activity and mineralization capacity of stress-treated SCAPs were upregulated . In the meantime, higher odontogenic and osteogenic differentiation were found in stress-treated SCAPs by real-time RT-PCR and Western blot, as indicated by the expression of related markers at both mRNA and protein levels. Moreover, the protein expressions of pJNK and pERK MAPK pathways were upregulated.Conclusion. Together, these findings suggest that mechanical stress is an important factor affecting the proliferation and differentiation of SCAPs via the activation of ERK and JNK signaling pathway.

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Junjun Li ◽  
Ming Yan ◽  
Zilu Wang ◽  
Shuanglin Jing ◽  
Yao Li ◽  
...  

Background Information. NF-κB signaling pathway plays a complicated role in the biological functions of mesenchymal stem cells. However, the effects of NF-κB pathway on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) remain unclear. The present study was designed to evaluate the effects of canonical NF-κB pathway on the osteo/odontogenic capacity of SCAPsin vitro.Results. Western blot results demonstrated that NF-κB pathway in SCAPs was successfully activated by TNF-αor blocked by BMS-345541. NF-κB pathway-activated SCAPs presented a higher proliferation activity compared with control groups, as indicated by dimethyl-thiazol-diphenyl tetrazolium bromide assay (MTT) and flow cytometry assay (FCM). Wound scratch assay revealed that NF-κB pathway-activated SCAPs presented an improved migration capacity, enhanced alkaline phosphatase (ALP) activity, and upregulated mineralization capacity of SCAPs, as compared with control groups. Meanwhile, the odonto/osteogenic markers (ALP/ALP,RUNX2/RUNX2,OSX/OSX,OCN/OCN,OPN/OPN,BSP/BSP,DSPP/DSP, andDMP-1/DMP-1) in NF-κB pathway-activated SCAPs were also significantly upregulated as compared with control groups at both protein and mRNA levels. However, NF-κB pathway-inhibited SCAPs exhibited a lower proliferation/migration capacity, and decreased odonto/osteogenic ability in comparison with control groups.Conclusion. Our findings suggest that classical NF-κB pathway plays a paramount role in the proliferation and committed differentiation of SCAPs.


2015 ◽  
Vol 332 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Jing Zhang ◽  
Zhihua Wang ◽  
Yong Jiang ◽  
Zhongying Niu ◽  
Lei Fu ◽  
...  

Author(s):  
Diana B. Sequeira ◽  
Ana Rafaela Oliveira ◽  
Catarina M. Seabra ◽  
Paulo J. Palma ◽  
Carlos Ramos ◽  
...  

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Qian Li ◽  
Xiwen Sun ◽  
Yunyi Tang ◽  
Yanan Qu ◽  
Yanheng Zhou ◽  
...  

Abstract Despite the ubiquitous mechanical cues at both spatial and temporal dimensions, cell identities and functions are largely immune to the everchanging mechanical stimuli. To understand the molecular basis of this epigenetic stability, we interrogated compressive force-elicited transcriptomic changes in mesenchymal stem cells purified from human periodontal ligament (PDLSCs), and identified H3K27me3 and E2F signatures populated within upregulated and weakly downregulated genes, respectively. Consistently, expressions of several E2F family transcription factors and EZH2, as core methyltransferase for H3K27me3, decreased in response to mechanical stress, which were attributed to force-induced redistribution of RB from nucleoplasm to lamina. Importantly, although epigenomic analysis on H3K27me3 landscape only demonstrated correlating changes at one group of mechanoresponsive genes, we observed a genome-wide destabilization of super-enhancers along with aberrant EZH2 retention. These super-enhancers were tightly bounded by H3K27me3 domain on one side and exhibited attenuating H3K27ac deposition and flattening H3K27ac peaks along with compensated EZH2 expression after force exposure, analogous to increased H3K27ac entropy or decreased H3K27ac polarization. Interference of force-induced EZH2 reduction could drive actin filaments dependent spatial overlap between EZH2 and super-enhancers and functionally compromise the multipotency of PDLSC following mechanical stress. These findings together unveil a specific contribution of EZH2 reduction for the maintenance of super-enhancer stability and cell identity in mechanoresponse.


Author(s):  
Yanchang Liu ◽  
Wendan Cheng ◽  
Yao Zhao ◽  
Liang Gao ◽  
Yongyun Chang ◽  
...  

Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.


Materials ◽  
2020 ◽  
Vol 13 (4) ◽  
pp. 974 ◽  
Author(s):  
José Luis Sanz ◽  
Leopoldo Forner ◽  
Alicia Almudéver ◽  
Julia Guerrero-Gironés ◽  
Carmen Llena

Blood clot formation in the apical third of the root canal system has been shown to promote further root development and reinforcement of dentinal walls by the deposition of mineralized tissue, resulting in an advancement from traditional apexification procedures to a regenerative endodontic treatment (RET) for non-vital immature permanent teeth. Silicate-based hydraulic biomaterials, categorized as bioactive endodontic cements, emerged as bright candidates for their use in RET as coronal barriers, sealing the previously induced blood clot scaffold. Human stem cells from the apical papilla (hSCAPs) surviving the infection may induce or at least be partially responsible for the regeneration or repair shown in RET. The aim of this study is to present a qualitative synthesis of available literature consisting of in vitro assays which analyzed the viability and stimulation of hSCAPs induced by silicate-based hydraulic biomaterials. A systematic electronic search was carried out in Medline, Scopus, Embase, Web of Science, Cochrane and SciELO databases, followed by a study selection, data extraction, and quality assessment following the PRISMA protocol. In vitro studies assessing the viability, proliferation, and/or differentiation of hSCAPs as well as their mineralization potential and/or osteogenic, odontogenic, cementogenic and/or angiogenic marker expression in contact with commercially available silicate-based materials were included in the present review. The search identified 73 preliminary references, of which 10 resulted to be eligible for qualitative synthesis. The modal materials studied were ProRoot MTA and Biodentine. Both bioceramic materials showed significant positive results when compared to a control for hSCAP cell viability, migration, and proliferation assays; a significant up-regulation of hSCAP odontogenic/osteogenic marker (ALP, DSPP, BSP, Runx2, OCN, OSX), angiogenic growth factor (VEGFA, FIGF) and pro-inflammatory cytokine (IL-1α, IL-1β, IL-6, TNF-α) expression; and a significant increase in hSCAP mineralized nodule formation assessed by Alizarin Red staining. Commercially available silicate-based materials considered in the present review can potentially induce mineralization and odontogenic/osteogenic differentiation of hSCAPs, thus prompting their use in regenerative endodontic procedures.


2017 ◽  
Vol 19 (2) ◽  
pp. 132-144 ◽  
Author(s):  
Hossein Yazdekhasti ◽  
Marzieh Agha Hosseini ◽  
Zahra Rajabi ◽  
Soraya Parvari ◽  
Mojdeh Salehnia ◽  
...  

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