• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.2
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• pp.73-81
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• 2013

Purpose: Smad4 is a central mediator for transforming growth factor-${\beta}$/bone morphogenetic protein ($TGF-{\beta}/BMP$) signals, which are involved in regulating cranial neural crest cell formation, migration, proliferation, and fate determination. Accumulated evidences indicate that $TGF-{\beta}/BMP$ signaling plays key roles in the early tooth morphogenesis. However, their roles in the late tooth formation, such as cellular differentiation and matrix formation are not clearly understood. The objective of this study is to understand the roles of Smad4 in vivo during enamel and dentin formation through tissue-specific inactivation of Smad4. Methods: We generated and analyzed mice with dental epithelium-specific inactivation of the Smad4 gene (K14-Cre:$Smad4^{fl/fl}$) and dental mesenchyme-specific inactivation of Smad4 gene (Osr2Ires-Cre:$Smad4^{fl/fl}$). Results: In the tooth germs of K14-Cre:$Smad4^{fl/fl}$, ameloblast differentiation was not detectable in inner enamel epithelial cells, however, dentin-like structure was formed in dental mesenchymal cells. In the tooth germs of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice, ameloblasts were normally differentiated from inner enamel epithelial cells. Interestingly, we found that bone-like structures, with cellular inclusion, were formed in the dentin region of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice. Conclusion: Taken together, our study demonstrates that Smad4 plays a crucial role in regulating ameloblast and odontoblast differentiation, as well as in regulating epithelial-mesenchymal interactions during tooth development.

• International Journal of Oral Biology
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• v.40 no.4
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• pp.197-204
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• 2015

MicroRNA (miRNA, miR) is essential in regulating cell differentiation either by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNA in odontoblastic cell differentiation is still unclear. In this study, we examined the molecular mechanism of miR-27-mediated regulation of odontoblast differentiation in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. The results of the present study demonstrated that the miR-27 expression increases significantly during MDPC-23 odontoblastic cell differentiation. Furthermore, miR-27 up-regulation promotes the differentiation of MDPC-23 cells and accelerates mineralization without cell proliferation. The over-expression of miR-27 significantly increased the expression levels of Wnt1 mRNA and protein. In addition, the results of target gene prediction revealed that Wnt1 mRNA has an miR-27 binding site in its 3'UTR, and is increased by miR-27. These results suggested that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting Wnt1 signaling. Therefore, miR-27 is a critical odontoblastic differentiation molecular target for the development of miRNA based therapeutic agents in dental medicine.

• Restorative Dentistry and Endodontics
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• v.41 no.1
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• pp.44-54
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• 2016

Objectives: The purpose of this study was to evaluate the histopathological effects of an antioxidant therapy on the pulp tissue of rat teeth exposed to a bleaching gel with 35% hydrogen peroxide. Materials and Methods: Forty rats were subjected to oral ingestion by gavage of distilled water (DW) or ascorbic acid (AA) 90 min before the bleaching therapy. For the bleaching treatment, the agent was applied twice for 5 min each to buccal surfaces of the first right mandibular molars. Then, the animals were sacrificed at 6 hr, 24 hr, 3 day, or 7 day post-bleaching, and the teeth were processed for microscopic evaluation of the pulp tissue. Results: At 6 hr, the pulp tissue showed moderate inflammatory reactions in all teeth of both groups. In the DW and AA groups, 100% and 80% of teeth exhibited pulp tissue with significant necrosis and intense tissue disorganization, respectively. At 24 hr, the AA-treated group demonstrated a greater regenerative capability than the DW group, with less intense inflammatory reaction and new odontoblast layer formation in 60% of the teeth. For up to the 7 day period, the areas of pulpal necrosis were replaced by viable connective tissue, and the dentin was underlined by differentiated odontoblast-like cells in most teeth of both groups. Conclusions: A slight reduction in initial pulpal damage during post-bleaching was promoted by AA therapy. However, the pulp tissue of AA-treated animals featured faster regenerative potential over time.

• International Journal of Oral Biology
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• v.43 no.3
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• pp.133-140
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• 2018

Resveratrol (3,4',5,-trihydroxystilbene), a phytoalexin present in grapes, exerts a variety of actions to reduce superoxides, prevents diabetes mellitus, and inhibits inflammation. Resveratrol acts as a chemo-preventive agent and induces apoptotic cell death in various cancer cells. However, the role of resveratrol in odontoblastic cell differentiation is unclear. In this study, the effect of resveratrol on regulating odontoblast differentiation was examined in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. Resveratrol significantly accelerated mineralization as compared with the control culture in differentiation of MDPC-23 cells. Resveratrol significantly increased expression of ALP mRNA as compared with the control in differentiation of MDPC-23 cells. Resveratrol significantly accelerated expression of Col I mRNA as compared with the control in differentiation of MDPC-23 cells. Resveratrol significantly increased expressions of DSPP and DMP-1 mRNAs as compared with the control in differentiation of MDPC-23 cells. Treatment of resveratrol did not significantly affect cell proliferation in MDPC-23 cells. Results suggest resveratrol facilitates odontoblast differentiation and mineralization in differentiation of MDPC-23 cells, and may have potential properties for development and clinical application of dentin regeneration materials.

• Journal of dental hygiene science
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• v.9 no.4
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• pp.427-433
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• 2009

Nuclear factor I-C (NFI-C) null mice demonstrated aberrant odontoblast differentiation and abnormal dentin formation. In order to elucidate the mechanisms responsible for these changes, we evaluated the expression of dentin matrix gene after over-expression and inactivation of NFI-C in MDPC-23 cells by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Collagen type I (Col I), osteocalcin (OC), and dentin sialophosphoprotein (DSPP) expression was decreased after inactivation of NFI-C. However, bone sialoprotein (BSP) expression was dramatically increased after inactivation of NFI-C. ALP and DMP4 expression was not changed after inactivation of NFI-C. The expression of alkaline phoshatase (ALP) and dentin matrix protein 4 (DMP4) was increased after over-expression of NFI-C, while Col I, OC, DSPP, and BSP expression was decreased. These findings suggest that odontoblasts after loss of NFI-C lost the phenotype of odontoblasts and acquired those of osteoblasts.

• Applied Microscopy
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• v.36 no.1
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• pp.17-23
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• 2006

The pregnant rats were given a drinking water administration of the sodium fluoride and normal saline for control animals. The sodium fluoride produced cellular changes of odontoblast with consistent response. Compare to control group, the odontoblasts that were administrated by sodium fluoride, showed significantly ultrastructural differences including large number of free ribosomes and swelled mitochondria in dose-dependent manner (300 ppm). From fine structural and morphological investigations of the changes in odontoblast, there were three distinctive structural changes: (1) destruction of the endoplasmic reticulum, (2) swelling of the mitochondria, and (3) severe cellular derangement of the endoplasmic reticulum and mitochondria. From this consecutive structural change, we observed that sodium fluoride temporarily affects the cell organelles in odontoblasts (100, 200 ppm), suggesting it is important that optimal concentration of the sodium fluoride in developing fetus of the rat.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.1
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• pp.37-45
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• 2022

The aim of the present study was to investigate the physiological role of nicotinamide phosphoribosyltransferase (NAMPT) associated with odontogenic differentiation during tooth development in mice. Mouse dental papilla cell-23 (MDPC-23) cells cultured in differentiation media were stimulated with the specific NAMPT inhibitor, FK866, and Visfatin (NAMPT) for up to 10 days. The cells were evaluated after 0, 4, 7, and 10 days. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mineralization assay was performed by staining MDPC-23 cells with Alizarin Red S solution. After cultivation, MDPC-23 cells were harvested for quantitative PCR or Western blotting. Analysis of variance was performed using StatView 5.0 software (SAS Institute Inc., Cary, NC, USA). Statistical significance was set at p < 0.05. The expression of NAMPT increased during the differentiation of murine odontoblast-like MDPC-23 cells. Furthermore, the up-regulation of NAMPT promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers, such as dentin sialophosphoprotein, dentin matrix protein-1, and alkaline phosphatase in MDPC-23 cells. However, treatment of the cells with the NAMPT inhibitor, FK866, attenuated odontogenic differentiation, as evidenced by the suppression of odontoblastic biomarkers. These data indicate that NAMPT regulated odontoblastic differentiation through the regulation of odontoblastic biomarkers. The increase in NAMPT expression in odontoblasts was closely related to the formation of the extracellular matrix and dentin via the Runx signaling pathway. Therefore, these data suggest that NAMPT is a critical regulator of odontoblast differentiation during tooth development.

• Journal of the korean academy of Pediatric Dentistry
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• v.32 no.3
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• pp.576-583
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• 2005

Tooth formation is a complex developmental process that is mediated through a series of reciprocal epithelial-mesenchymal interactions. Several signal pathways and transcription factors have been implicated in regulating molar crown development, but relatively little is known about the regulation of root development. It was reported that NFI-C knockout mice showed abnormal root formation with normal crown. The aims of this study are to elucidate how the NFI-C regulate the determine of root shape and odontoblasts differentiation. We carried out immunohistochemistry using cytokeratin to investigate the role of Hertwig's epithelial root sheath and DSPP mRNA in-situ hybridization to conform the nature of root dentin during root development in NFI-C knockout mice. Cytokeratin reacted with all the HERS cells and the continuity of cytokeratin positive cells between the HERS cells and enamel epithelium was lost in the cervical region both wild and K/O types. After root dentin deposition cytokeratin positive-HERS cells showed irregularity and loss of polarity in the cervical region in K/O type. DSPP mRNA was strongly expressed in odontoblasts of crown and root dentin in wild type mice, whereas expression of DSPP mRNA was restricted in odontoblast of crown dentin in the K/O type. During root formation in NFI-C knockout mice, HERS normally grow out of the crown but fail to induce odontoblast differentiation in root portion. These results suggest that NFI-C may play important roles in odontoblast differentiation during root dentin formation.

• The Journal of the Korean dental association
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• v.11 no.3
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• pp.199-203
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• 1973

Various concentration of formaldehyde solution (1%, 5%, 10%) were applied to cut pulp surface, for 3 minutes and the remaining pulp were carefully examined histo-pathologically. The result were as follows, 1. One week survival group which were treated by 1% formaldehyde solution showed seperation of odontoblast layer randomly and the weil's zone was undistinguishable. Deeper portion of this area was necrotic or coagulated. 2. Two week survival group which were treated 1% formaldehyde solution showed necrotic appearance spread from odontoblastic layer to weil's zone. 3. One and two week survival group which were treated 5% formaldehyde solution showed the odontoblastic layer was highly necrotic, under this zone empty net-work was seen. 4. One and two week survival group treated 10% formaldehyde solution showed complete destruction of pulp.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.43 no.2
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• pp.63-69
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• 2017

Nuclear factor I-C (NFI-C) plays a pivotal role in various cellular processes such as odontoblast and osteoblast differentiation. Nfic-deficient mice showed abnormal tooth and bone formation. The transplantation of Nfic-expressing mouse bone marrow stromal cells rescued the impaired bone formation in $Nfic^{-/-}$ mice. Studies suggest that NFI-C regulate osteogenesis and dentinogenesis in concert with several factors including transforming growth factor-${\beta}1$, $Kr{\ddot{u}}ppel$-like factor 4, and ${\beta}$-catenin. This review will focus on the function of NFI-C during tooth and bone formation and on the relevant pathways that involve NFI-C.