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 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.

The Effect of TGF-β2 on Dentin Apposition and Hardness in Transgenic Mice

2001 ◽  
Vol 15 (1) ◽  
pp. 39-41 ◽  
Author(s):  
P.K. DenBesten ◽  
Darren Machule ◽  
Richard Gallagher ◽  
Grayson W. Marshall ◽  
Catherina Mathews ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mineral Apposition Rate ◽  
Tooth Formation ◽  
Reparative Dentin ◽  
Mineralized Tissues ◽  
Tooth Repair ◽  
Dentin Formation

Transforming growth factor β, TGF-β, is expressed during tooth formation and can induce pre-odontoblast differentiation and formation of functional odontoblast-like cells in vitro. In addition, exogenous TGF-β can increase reparative dentin formation, presumably by acting on odontoblasts. In this study, we examined the tooth phenotype of transgenic mice, in which TGF-β2 expression is directed by the osteocalcin promoter. Previous studies have shown that these mice have a bone phenotype that resembles that of human osteoporosis, including the existence of spontaneous fractures. Microhardness testing of the enamel and dentin showed no differences in the molars of these transgenic mice as compared with those of their wild-type littermates. Consistent with the increase in bone mineral apposition rate previously reported in these mice, the dentin apposition rate appeared to be increased in the TGF-β2-overexpressing mice. Thus, in teeth, as in bone, TGF-β2 appears to stimulate the synthesis and deposition of matrix. Further studies are needed to understand the effect of TGF-β2 on distinct mineralized tissues (bone, dentin, and cementum) and to determine whether exogenous TGF-β2 may be useful for tooth repair.

In Vivo Effects of Amelogenins on Reparative Dentin Formation

2012 ◽  
pp. 174-190 ◽  
Author(s):  
Yassine Harichane ◽  
Sasha Dimitrova-Nakov ◽  
Anne Poliard ◽  
Arthur Veis ◽  
Pamela DenBesten ◽  
...  
Keyword(s):  
Reparative Dentin ◽  
Dentin Formation ◽  
In Vivo Effects ◽  
Reparative Dentin Formation

scholarly journals Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Xu ◽  
Guiping Chen ◽  
Huaen Xu ◽  
Guoming Xia ◽  
Meisong Zhu ◽  
...  
Keyword(s):  
Bone Loss ◽  
Transforming Growth Factor ◽  
Osteoclast Formation ◽  
Mitogen Activated Protein Kinase ◽  
Mice Model ◽  
Titanium Particle ◽  
Ovariectomized Mice ◽  
Prosthetic Loosening

Excessive bone resorption by osteoclasts contributes significantly to osteoclast-related diseases such as periprosthetic osteolysis and osteoporosis. Osteolysis in a titanium particle-induced calvarial model and bone loss in an ovariectomized mice model occurred similarly to those in humans; thus, these models can be used to evaluate potential therapies for aseptic prosthetic loosening and osteoporosis. Celastrol, which is extracted from the seeds of the genus Tripterygium, has been thoroughly investigated for its anti-inflammatory and anti-cancer pharmacological effects. However, the mechanisms involving bone metabolism by which celastrol inhibits osteoclastogenesis are not yet fully understood. We demonstrated that celastrol inhibited the receptor activator of nuclear factor κB ligand-induced osteoclastogenesis and the bone resorptive function of osteoclasts in vitro by inhibiting the activation of transforming growth factor β-activated kinase 1-mediated NF-κB and mitogen-activated protein kinase signaling pathways and downregulating osteoclastogenesis marker-related genes. Furthermore, celastrol was also shown to be beneficial in both the titanium particle-induced osteolysis calvarial and the murine ovariectomy-induced bone loss. Collectively, our results suggested that celastrol is promising for the prevention of aseptic prosthetic loosening and osteoporosis in the treatment of osteolytic diseases induced by disrupted osteoclast formation and function.

scholarly journals Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1985
Author(s):  
Xiaohe Li ◽  
Ling Ma ◽  
Kai Huang ◽  
Yuli Wei ◽  
Shida Long ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
In Vivo Experiments ◽  
Age Related ◽  
And Migration ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

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