scholarly journals Retinoic Acid Signal Negatively Regulates Osteo/Odontogenic Differentiation of Dental Pulp Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jiangyi Wang ◽  
Guoqing Li ◽  
Lei Hu ◽  
Fei Yan ◽  
Bin Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Tissue Regeneration ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
Miniature Pigs ◽  
Odontogenic Differentiation

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.

scholarly journals miR-6807-5p Inhibited the Odontogenic Differentiation of Human Dental Pulp Stem Cells Through Directly Targeting METTL7A

2021 ◽  
Vol 9 ◽  
Author(s):  
Ning Wang ◽  
Xiao Han ◽  
Haoqing Yang ◽  
Dengsheng Xia ◽  
Zhipeng Fan
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Binding Protein ◽  
Dental Pulp Stem Cells ◽  
Luciferase Reporter ◽  
Control Group ◽  
Alizarin Red ◽  
Odontogenic Differentiation ◽  
Human Dental Pulp ◽  
Tooth Tissue

Background: Tooth tissue regeneration mediated by mesenchymal stem cells (MSCs) has become the most ideal treatment. Although the known regulatory mechanism and some achievements have been discovered, directional differentiation cannot effectively induce regeneration of tooth tissue. In this study, we intended to explore the function and mechanism of miR-6807-5p and its target gene METTL7A in odontogenic differentiation.Methods: In this study, human dental pulp stem cells (DPSCs) were used. Alkaline phosphatase (ALP), Alizarin red staining (ARS), and calcium ion quantification were used to detect the odontogenic differentiation of miR-6807-5p and METTL7A. Real-time RT-PCR, western blot, dual-luciferase reporter assay, and pull-down assay with biotinylated miRNA were used to confirm that METTL7A was the downstream gene of miR-6807-5p. Protein mass spectrometry and co-immunoprecipitation (Co-IP) were used to detect that SNRNP200 was the co-binding protein of METTL7A.Results: After mineralized induction, the odontogenic differentiation was enhanced in the miR-6807-5p-knockdown group and weakened in the miR-6807-5p-overexpressed group compared with the control group. METTL7A was the downstream target of miR-6807-5p. After mineralized induction, the odontogenic differentiation was weakened in the METTL7A-knockdown group and enhanced in the METTL7A-overexpressed group compared with the control group. SNRNP200 was the co-binding protein of METTL7A. The knockdown of SNRNP200 inhibited the odontogenic differentiation of DPSCs.Conclusion: This study verified that miR-6807-5p inhibited the odontogenic differentiation of DPSCs. The binding site of miR-6807-5p was the 3′UTR region of METTL7A, which was silenced by miR-6807-5p. METTL7A promoted the odontogenic differentiation of DPSCs. SNRNP200, a co-binding protein of METTL7A, promoted the odontogenic differentiation of DPSCs.

scholarly journals The Effect of Mesoporous Bioactive Glass Nanoparticles/Graphene Oxide Composites on the Differentiation and Mineralization of Human Dental Pulp Stem Cells

Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 620 ◽  
Author(s):  
Jae Hwa Ahn ◽  
In-Ryoung Kim ◽  
Yeon Kim ◽  
Dong-Hyun Kim ◽  
Soo-Byung Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Graphene Oxide ◽  
Bioactive Glass ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Mrna Levels ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
Human Dental Pulp ◽  
Mesoporous Bioactive Glass

The purpose of this study was to investigate the effects of mesoporous bioactive glass nanoparticle (MBN)/graphene oxide (GO) composites on the mineralization ability and differentiation potential of human dental pulp stem cells (hDPSCs). MBN/GO composites were synthesized using the sol-gel method and colloidal processing to enhance the bioactivity and mechanical properties of MBN. Characterization using FESEM, XRD, FTIR, and Raman spectrometry showed that the composites were successfully synthesized. hDPSCs were then cultured directly on the MBN/GO (40:1 and 20:1) composites in vitro. MBN/GO promoted the proliferation and alkaline phosphatase (ALP) activity of hDPSCs. In addition, qRT-PCR showed that MBN/GO regulated the mRNA levels of odontogenic markers (dentin sialophosphoprotein (DSPP), dentine matrix protein 1 (DMP-1), ALP, matrix extracellular phosphoglycoprotein (MEPE), bone morphogenetic protein 2 (BMP-2), and runt-related transcription factor 2 (RUNX-2)). The mRNA levels of DSPP and DMP-1, two odontogenesis-specific markers, were considerably upregulated in hDPSCs in response to growth on the MBN/GO composites. Western blot analysis revealed similar results. Alizarin red S staining was subsequently performed to further investigate MBN/GO-induced mineralization of hDPSCs. It was revealed that MBN/GO composites promote odontogenic differentiation via the Wnt/β-catenin signaling pathway. Collectively, the results of the present study suggest that MBN/GO composites may promote the differentiation of hDPSCs into odontoblast-like cells, and potentially induce dentin formation.

scholarly journals Insight into the Role of Dental Pulp Stem Cells in Regenerative Therapy

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 160 ◽  
Author(s):  
Shinichiro Yoshida ◽  
Atsushi Tomokiyo ◽  
Daigaku Hasegawa ◽  
Sayuri Hamano ◽  
Hideki Sugii ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tissue Regeneration ◽  
Dental Pulp ◽  
High Growth ◽  
Dental Pulp Stem Cells ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Pulp Tissue ◽  
Differentiation Potential ◽  
Cell Based Therapy

Mesenchymal stem cells (MSCs) have the capacity for self-renewal and multilineage differentiation potential, and are considered a promising cell population for cell-based therapy and tissue regeneration. MSCs are isolated from various organs including dental pulp, which originates from cranial neural crest-derived ectomesenchyme. Recently, dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) have been isolated from dental pulp tissue of adult permanent teeth and deciduous teeth, respectively. Because of their MSC-like characteristics such as high growth capacity, multipotency, expression of MSC-related markers, and immunomodulatory effects, they are suggested to be an important cell source for tissue regeneration. Here, we review the features of these cells, their potential to regenerate damaged tissues, and the recently acquired understanding of their potential for clinical application in regenerative medicine.

Simvastatin Induces the Odontogenic Differentiation of Human Dental Pulp Stem Cells In Vitro and In Vivo

2009 ◽  
Vol 35 (3) ◽  
pp. 367-372 ◽  
Author(s):  
Yosuke Okamoto ◽  
Wataru Sonoyama ◽  
Mitsuaki Ono ◽  
Kentaro Akiyama ◽  
Takuo Fujisawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Odontogenic Differentiation ◽  
Human Dental Pulp

scholarly journals Extracellular IL-37 Enhances Osteogenic and Odontogenic Differentiation of Human Dental Pulp Stem Cells via Autophagy Pathway

2021 ◽  
Author(s):  
Na Li ◽  
Yan Chen ◽  
Ming Yan ◽  
Yanqiu Wang ◽  
Jintao Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Inflammatory Factor ◽  
Alizarin Red ◽  
Dental Tissues ◽  
Alp Activity ◽  
Odontogenic Differentiation ◽  
Marrow Mesenchymal Stem Cells

Abstract BackgroundThe osteogenic and odontogenic differentiation of dental pulp stem cells (DPSCs) contributes to the restoration and regeneration of dental tissues. Previous study indicated that IL-37 has often been identified as an anti-inflammatory factor that affects other pro-inflammatory signals. It is known to be a factor capable of inducing in vitro osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). The aims of this study were to explore the effects of IL-37 on the differentiation of DPSCs.MethodsDPSCs were cultured in growth medium with different concentration of IL-37, ALP activity was done to detect the optimal concentration for the following experiments. CCK-8 were conducted to assess the effect of IL-37 on proliferation of DPSCs. To assess differentiation, alkaline phosphatase activity, ALP staining, alizarin red S staining and real‐time RT‐PCR of DSPP, Runx2, ALP, and OSX were measured. Western blot was conducted to examine the levels of autophagy related markers (Beclin1, P62, LC3). ResultsCells cultured with 1 ng/mL IL-37 owned the highest ALP activity. IL-37 enhanced the osteogenic and odontogenic differentiation of DPSCs following upregulated the expression of Beclin1, downregulated the expression of P62, and reduced the ratio of LC3II/I, whereas depletion of autophagy suppressed DPSCs osteogenic and odontogenic differentiation. ConclusionIL-37 increased osteogenic and odontogenic differentiation via autophagy.

scholarly journals Effects of Helioxanthin Derivative-Treated Human Dental Pulp Stem Cells on Fracture Healing

2020 ◽  
Vol 21 (23) ◽  
pp. 9158
Author(s):  
Daiki Yamakawa ◽  
Yoko Kawase-Koga ◽  
Yasuyuki Fujii ◽  
Yuki Kanno ◽  
Marika Sato ◽  
...  
Keyword(s):  
Stem Cells ◽  
Fracture Healing ◽  
Efficient Method ◽  
Dental Pulp ◽  
Fracture Site ◽  
Dental Pulp Stem Cells ◽  
Differentiation Potential ◽  
Normal Medium ◽  
Human Dental Pulp

Bone defects affect patients functionally and psychologically and can decrease quality of life. To resolve these problems, a simple and efficient method of bone regeneration is required. Human dental pulp stem cells (DPSCs) have high proliferative ability and multilineage differentiation potential. In our previous study, we reported a highly efficient method to induce osteogenic differentiation using DPSC sheets treated with a helioxanthin derivative (4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH)) in a mouse calvarial defect model. However, the localization of the DPSCs after transplantation remains unknown. Therefore, in this study, we investigated the localization of transplanted DPSCs in a mouse fracture model. DPSCs were collected from six healthy patients aged 18–29 years, cultured in normal medium (NM), osteogenic medium (OM), or OM with TH, and fabricated them into cell sheets. To evaluate the efficacy of fracture healing using DPSCs treated with OM+TH, and to clarify the localization of the transplanted DPSC sheets in vivo, we transplanted OM+TH-treated DPSC sheets labeled with PKH26 into mouse tibiae fractures. We demonstrated that transplanted OM+TH-treated DPSCs sheets were localized to the fracture site and facilitated bone formation. These results indicated that transplanted OM+TH-treated DPSCs were localized at fracture sites and directly promoted fracture healing.

Effects of Recombinant Overexpression of Bcl2 on the Proliferation, Apoptosis, and Osteogenic/Odontogenic Differentiation Potential of Dental Pulp Stem Cells

2016 ◽  
Vol 42 (4) ◽  
pp. 575-583 ◽  
Author(s):  
Boon Chin Heng ◽  
Xin Ye ◽  
Yuan Liu ◽  
Waruna Lakmal Dissanayaka ◽  
Gary Shun Pan Cheung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Differentiation Potential ◽  
Odontogenic Differentiation

scholarly journals Depletion of EREG enhances the osteo/dentinogenic differentiation ability of dental pulp stem cells via the p38 MAPK and Erk pathways in an inflammatory microenvironment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ran Ran ◽  
Haoqing Yang ◽  
Yangyang Cao ◽  
Wanhao Yan ◽  
Luyuan Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
P38 Mapk ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Signalling Pathways ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Dentinogenic Differentiation

Abstract Background Epiregulin (EREG) is an important component of EGF and was demonstrated to promote the osteo/dentinogenic differentiation of stem cells from dental apical papilla (SCAPs). Whether EREG can stimulate the osteo/dentinogenic differentiation of dental pulp stem cells (DPSCs) in inflammatory environment is not clear. The purpose of the present study is to investigate the role of EREG on the osteo/dentinogenic differentiation ability of DPSCs in inflammatory environment. Methods DPSCs were isolated from human third molars. Short hairpin RNAs (shRNAs) were used to knock down EREG expression in DPSCs. Recombinant human EREG (rhEREG) protein was used in the rescue experiment. TNF-α was employed to mimic the inflammatory environment in vitro. Alkaline phosphatase (ALP) staining, Alizarin red staining, quantitative calcium analysis, and real-time RT-PCR were performed to detect osteo/dentinogenic differentiation markers and related signalling pathways under normal and inflammatory conditions. Results EREG depletion promoted the ALP activity and mineralization ability of DPSCs. The expression of BSP, DMP-1, and DSPP was also enhanced. Moreover, 50 ng/mL rhEREG treatment decreased the osteo/dentinogenic differentiation potential of DPSCs, while treatment with 10 ng/mL TNF-α for 4 h increased the expression of EREG in DPSCs. Conversely, EREG knockdown rescued the impaired osteo/dentinogenic differentiation ability caused by TNF-α treatment. Further mechanistic studies showed that EREG depletion activated the p38 MAPK and Erk signalling pathways in DPSCs under normal and inflammatory conditions. Conclusions Our results demonstrated that EREG could inhibit the osteo/dentinogenic differentiation potential of DPSCs via the p38 MAPK and Erk signalling pathways. Under inflammatory environment, EREG depletion enhanced osteo/dentinogenic differentiation potential of DPSCs by improving the expression of p-p38 MAPK and p-Erk.

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