scholarly journals Lithium Chloride Exerts Differential Effects on Dentinogenesis and Osteogenesis in Primary Pulp Cultures

2021 ◽  
Vol 2 ◽  
Author(s):  
Anushree Vijaykumar ◽  
Mina Mina
Keyword(s):  
Dental Pulp ◽  
Osteoblast Differentiation ◽  
Prolonged Treatment ◽  
Odontoblast Differentiation ◽  
Positive Effects ◽  
Reparative Dentin ◽  
Dentin Formation ◽  
Reparative Dentin Formation

Wnt/β-catenin signaling is known to play essential roles in odontoblast differentiation and reparative dentin formation. Various Wnt activators including LiCl have been increasingly studied for their effectiveness to induce repair of the dentin-pulp complex. LiCl is a simple salt thought to activate Wnt/β-catenin signaling by inhibiting GSK3β. Previous in vitro and in vivo studies showed that LiCl increased odontoblast differentiation and enhanced reparative dentin formation. However, the underlying molecular and cellular mechanisms by which LiCl regulates odontoblast and osteoblast differentiation during reparative dentinogenesis are not well-understood. Our in vitro studies show that exposure of early dental pulp progenitors to LiCl increased the survival and the pool of αSMA+ progenitors, leading to enhanced odontoblast and osteoblast differentiation. The positive effects of LiCl in the differentiation of osteoblasts and odontoblasts from αSMA+ progenitors are mediated by Wnt/β-catenin signaling. Our results also showed that continuous and late exposure of dental pulp cells to LiCl increased the expression of odontoblast markers through Wnt/β-catenin signaling, and the number of odontoblasts expressing DMP1-Cherry and DSPP-Cerulean transgenes. However, unlike the early treatment, both continuous and late treatments decreased the expression of Bsp and the expression of BSP-GFPtpz transgene. These observations suggest that prolonged treatment with LiCl in more mature cells of the dental pulp has an inhibitory effect on osteoblast differentiation. The inhibitory effects of LiCl on osteogenesis and Bsp were not mediated through Wnt/β-catenin signaling. These observations suggest that the effects of LiCl, and GSK3β antagonists on reparative dentinogenesis involve multiple pathways and are not specific to Wnt/β-catenin signaling.

scholarly journals Dentin Phosphophoryn-Derived Peptide Promotes Odontoblast Differentiation In Vitro and Dentin Regeneration In Vivo

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 874
Author(s):  
Bayarchimeg Altankhishig ◽  
Mohammad Ali Akbor Polan ◽  
Youjing Qiu ◽  
Md Riasat Hasan ◽  
Takashi Saito
Keyword(s):  
Calcium Hydroxide ◽  
Alizarin Red ◽  
Odontoblast Differentiation ◽  
Reparative Dentin ◽  
Pulp Inflammation ◽  
Dentin Formation ◽  
Reparative Dentin Formation ◽  
Dentin Regeneration

The purpose of the present study was to investigate the effect of a peptide (i.e., SESDNNSSSRGDASYNSDES) derived from dentin phosphophoryn (DPP) with arginine-glycine-aspartic acid (RGD) motifs on odontoblast differentiation in vitro and to compare it with calcium hydroxide—a material used conventionally for vital pulp therapy—in terms of reparative dentin formation and pulp inflammation in vivo. Alkaline phosphatase activity assay and alizarin red S staining were performed to evaluate odontoblast-differentiation in cell culturing experiments. To observe the reparative dentin formation and pulp inflammation animal experiment was performed and examined by histological methods. The difference between the experimental group and the control group was analyzed statistically using a one-way ANOVA test. The results revealed that the DPP-derived RGD-containing peptide triggered odontoblast differentiation and mineralization in vitro. In rats undergoing direct pulp capping, the DPP-derived RGD-containing peptide was found to induce intensively formed reparative dentin with high compactness at week 4. On histological and morphometrical examinations, a smaller degree of pulpitis was observed in the specimens treated with the peptide than in those treated with calcium hydroxide. This study suggests that the DPP-derived RGD-containing peptide is a biocompatible, biodegradable and bioactive material for dentin regeneration.

scholarly journals Facilitating Reparative Dentin Formation Using Apigenin Local Delivery in the Exposed Pulp Cavity

2021 ◽  
Vol 12 ◽  
Author(s):  
Yam Prasad Aryal ◽  
Chang-Yeol Yeon ◽  
Tae-Young Kim ◽  
Eui-Seon Lee ◽  
Shijin Sung ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Traumatic Injury ◽  
Local Delivery ◽  
Protease Production ◽  
Mice Model ◽  
Reparative Dentin ◽  
Dentin Formation ◽  
Reparative Dentin Formation

Apigenin, a natural product belonging to the flavone class, affects various cell physiologies, such as cell signaling, inflammation, proliferation, migration, and protease production. In this study, apigenin was applied to mouse molar pulp after mechanically pulpal exposure to examine the detailed function of apigenin in regulating pulpal inflammation and tertiary dentin formation. In vitro cell cultivation using human dental pulp stem cells (hDPSCs) and in vivo mice model experiments were employed to examine the effect of apigenin in the pulp and dentin regeneration. In vitro cultivation of hDPSCs with apigenin treatment upregulated bone morphogenetic protein (BMP)- and osteogenesis-related signaling molecules such as BMP2, BMP4, BMP7, bone sialoprotein (BSP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN) after 14 days. After apigenin local delivery in the mice pulpal cavity, histology and cellular physiology, such as the modulation of inflammation and differentiation, were examined using histology and immunostainings. Apigenin-treated specimens showed period-altered immunolocalization patterns of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), NESTIN, and transforming growth factor (TGF)-β1 at 3 and 5 days. Moreover, the apigenin-treated group showed a facilitated dentin-bridge formation with few irregular tubules after 42 days from pulpal cavity preparation. Micro-CT images confirmed obvious dentin-bridge structures in the apigenin-treated specimens compared with the control. Apigenin facilitated the reparative dentin formation through the modulation of inflammation and the activation of signaling regulations. Therefore, apigenin would be a potential therapeutic agent for regenerating dentin in exposed pulp caused by dental caries and traumatic injury.

scholarly journals FGF2 Enhances Odontoblast Differentiation by αSMA+ Progenitors In Vivo

2018 ◽  
Vol 97 (10) ◽  
pp. 1170-1177 ◽  
Author(s):  
I. Vidovic-Zdrilic ◽  
K.H. Vining ◽  
A. Vijaykumar ◽  
I. Kalajzic ◽  
D.J. Mooney ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Dental Pulp ◽  
Lineage Tracing ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Odontoblast Differentiation ◽  
Reparative Dentin

The goal of this study was to examine the effects of early and limited exposure of perivascular cells expressing α (αSMA) to fibroblast growth factor 2 (FGF2) in vivo. We performed in vivo fate mapping by inducible Cre-loxP and experimental pulp injury in molars to induce reparative dentinogenesis. Our results demonstrate that early delivery of exogenous FGF2 to exposed pulp led to proliferative expansion of αSMA-tdTomato+ cells and their accelerated differentiation into odontoblasts. In vivo lineage-tracing experiments showed that the calcified bridge/reparative dentin in FGF2-treated pulps were lined with an increased number of Dspp+ odontoblasts and devoid of BSP+ osteoblasts. The increased number of odontoblasts derived from αSMA-tdTomato+ cells and the formation of reparative dentin devoid of osteoblasts provide in vivo evidence for the stimulatory effects of FGF signaling on odontoblast differentiation from early progenitors in dental pulp.

scholarly journals Dental Pulp Defence and Repair Mechanisms in Dental Caries

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Jean-Christophe Farges ◽  
Brigitte Alliot-Licht ◽  
Emmanuelle Renard ◽  
Maxime Ducret ◽  
Alexis Gaudin ◽  
...  
Keyword(s):  
Dental Caries ◽  
Dental Pulp ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Oral Bacteria ◽  
Barrier Formation ◽  
Reparative Dentin ◽  
Pulp Inflammation

Dental caries is a chronic infectious disease resulting from the penetration of oral bacteria into the enamel and dentin. Microorganisms subsequently trigger inflammatory responses in the dental pulp. These events can lead to pulp healing if the infection is not too severe following the removal of diseased enamel and dentin tissues and clinical restoration of the tooth. However, chronic inflammation often persists in the pulp despite treatment, inducing permanent loss of normal tissue and reducing innate repair capacities. For complete tooth healing the formation of a reactionary/reparative dentin barrier to distance and protect the pulp from infectious agents and restorative materials is required. Clinical andin vitroexperimental data clearly indicate that dentin barrier formation only occurs when pulp inflammation and infection are minimised, thus enabling reestablishment of tissue homeostasis and health. Therefore, promoting the resolution of pulp inflammation may provide a valuable therapeutic opportunity to ensure the sustainability of dental treatments. This paper focusses on key cellular and molecular mechanisms involved in pulp responses to bacteria and in the pulpal transition between caries-induced inflammation and dentinogenic-based repair. We report, using selected examples, different strategies potentially used by odontoblasts and specialized immune cells to combat dentin-invading bacteriain vivo.

scholarly journals Silencing VEGFR-2 Hampers Odontoblastic Differentiation of Dental Pulp Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Kajohnkiart Janebodin ◽  
Rakchanok Chavanachat ◽  
Aislinn Hays ◽  
Morayma Reyes Gil
Keyword(s):  
Stem Cells ◽  
Blood Vessels ◽  
Dental Pulp ◽  
Alizarin Red ◽  
Odontoblast Differentiation ◽  
Dentin Matrix ◽  
Dentin Regeneration

Dental pulp stem cells (DPSCs) are a source of postnatal stem cells essential for maintenance and regeneration of dentin and pulp tissues. Previous in vivo transplantation studies have shown that DPSCs are able to give rise to odontoblast-like cells, form dentin/pulp-like structures, and induce blood vessel formation. Importantly, dentin formation is closely associated to blood vessels. We have previously demonstrated that DPSC-induced angiogenesis is VEGFR-2-dependent. VEGFR-2 may play an important role in odontoblast differentiation of DPSCs, tooth formation and regeneration. Nevertheless, the role of VEGFR-2 signaling in odontoblast differentiation of DPSCs is still not well understood. Thus, in this study we aimed to determine the role of VEGFR-2 in odontoblast differentiation of DPSCs by knocking down the expression of VEGFR-2 in DPSCs and studying their odontoblast differentiation capacity in vitro and in vivo. Isolation and characterization of murine DPSCs was performed as previously described. DPSCs were induced by VEGFR-2 shRNA viral vectors transfection (MOI = 10:1) to silence the expression of VEGFR-2. The GFP+ expression in CopGFP DPSCs was used as a surrogate to measure the efficiency of transfection and verification that the viral vector does not affect the expression of VEGFR-2. The efficiency of viral transfection was shown by significant reduction in the levels of VEGFR-2 based on the Q-RT-PCR and immunofluorescence in VEGFR-2 knockdown DPSCs, compared to normal DPSCs. VEGFR-2 shRNA DPSCs expressed not only very low level of VEGFR-2, but also that of its ligand, VEGF-A, compared to CopGFP DPSCs in both transcriptional and translational levels. In vitro differentiation of DPSCs in osteo-odontogenic media supplemented with BMP-2 (100 ng/ml) for 21 days demonstrated that CopGFP DPSCs, but not VEGFR-2 shRNA DPSCs, were positive for alkaline phosphatase (ALP) staining and formed mineralized nodules demonstrated by positive Alizarin Red S staining. The expression levels of dentin matrix proteins, dentin matrix protein-1 (Dmp1), dentin sialoprotein (Dspp), and bone sialoprotein (Bsp), were also up-regulated in differentiated CopGFP DPSCs, compared to those in VEGFR-2 shRNA DPSCs, suggesting an impairment of odontoblast differentiation in VEGFR-2 shRNA DPSCs. In vivo subcutaneous transplantation of DPSCs with hydroxyapatite (HAp/TCP) for 5 weeks demonstrated that CopGFP DPSCs were able to differentiate into elongated and polarized odontoblast-like cells forming loose connective tissue resembling pulp-like structures with abundant blood vessels, as demonstrated by H&E, Alizarin Red S, and dentin matrix staining. On the other hand, in VEGFR-2 shRNA DPSC transplants, odontoblast-like cells were not observed. Collagen fibers were seen in replacement of dentin/pulp-like structures. These results indicate that VEGFR-2 may play an important role in dentin regeneration and highlight the potential of VEGFR-2 modulation to enhance dentin regeneration and tissue engineering as a promising clinical application.

scholarly journals Secreted Frizzled-Related Protein 1 Promotes Odontoblastic Differentiation and Reparative Dentin Formation in Dental Pulp Cells

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2491
Author(s):  
Keita Ipposhi ◽  
Atsushi Tomokiyo ◽  
Taiga Ono ◽  
Kozue Yamashita ◽  
Muhammad Anas Alhasan ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Nodule Formation ◽  
Dental Pulp Cells ◽  
Related Protein ◽  
Direct Pulp Capping ◽  
Odontoblastic Differentiation ◽  
Reparative Dentin ◽  
Pulp Cells ◽  
Dentin Formation ◽  
Reparative Dentin Formation

Direct pulp capping is an effective treatment for preserving dental pulp against carious or traumatic pulp exposure via the formation of protective reparative dentin by odontoblast-like cells. Reparative dentin formation can be stimulated by several signaling molecules; therefore, we investigated the effects of secreted frizzled-related protein (SFRP) 1 that was reported to be strongly expressed in odontoblasts of newborn molar tooth germs on odontoblastic differentiation and reparative dentin formation. In developing rat incisors, cells in the dental pulp, cervical loop, and inner enamel epithelium, as well as ameloblasts and preodontoblasts, weakly expressed Sfrp1; however, Sfrp1 was strongly expressed in mature odontoblasts. Human dental pulp cells (hDPCs) showed stronger expression of SFRP1 compared with periodontal ligament cells and gingival cells. SFRP1 knockdown in hDPCs abolished calcium chloride-induced mineralized nodule formation and odontoblast-related gene expression and decreased BMP-2 gene expression. Conversely, SFRP1 stimulation enhanced nodule formation and expression of BMP-2. Direct pulp capping treatment with SFRP1 induced the formation of a considerable amount of reparative dentin that has a structure similar to primary dentin. Our results indicate that SFRP1 is crucial for dentinogenesis and is important in promoting reparative dentin formation in response to injury.

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