Dental Papilla Research Articles

Establishment of an Immortalized Mouse Bmp2 Knockout Dental Papilla Mesenchymal Cell Line.

Bone morphogenetic protein 2 (Bmp2) is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta (DGI), showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. Here we describe the generation of an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2ko/ko-dp) cell line by introducing Cre fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2flox/flox-dp) cells.

Improvement of Cell Viability Using a Rho-associated Protein Kinase (ROCK) Inhibitor in Human Dental Papilla derived Single-induced Pluripotent Stem Cells

Improvement of Cell Viability Using a Rho-associated Protein Kinase (ROCK) Inhibitor in Human Dental Papilla derived Single-induced Pluripotent Stem Cells

Apical Papilla Cells Are Capable of Forming a Pulplike Tissue with Odontoblastlike Cells without the Use of Exogenous Growth Factors

IntroductionDental pulp is a complex tissue with highly differentiated cells, which makes its reconstruction a challenging task. The apical papilla is an undifferentiated tissue considered as the remnant of the dental papilla that forms the dentin-pulp complex. Aiming to analyze morphologic features of the tissue formed in an in vivo pulp model, we used human apical papilla as a cell source without the use of exogenous growth factors. MethodsA construct was built using newborn mice molar crowns treated with TrypLE (Fisher Scientific, Loughborough, UK) and EDTA. The crowns were filled with PuraMatrix (Corning Inc, Corning, NY) and a pool population of human apical papilla cells. As a control, we used crowns filled only with PuraMatrix and empty crowns. The constructs were transplanted under severe combined immunodeficient mice kidney capsules. Immunohistochemistry for lamin A, dentin sialophosphoprotein, and dentin matrix protein 1 was performed. ResultsMorphologic analysis of all transplanted crowns showed the formation of a loose connective tissue of variable cellularity with the presence of well-formed functional vessels. In the study group, lamin A–positive cells represented the majority of cells within the pulp chamber and a few cells in the vessel lining. We also found positivity for dentin sialophosphoprotein and dentin matrix protein 1, an indicator of odontoblast differentiation. ConclusionsIn our study model, human transplanted apical papilla cells mixed with the host cells and formed a vascularized viable tissue, and these cells were able to differentiate into odontoblastlike cells without the use of exogenous growth factors.

Immunolocalization of transforming growth factor-beta1, connective tissue growth factor, phosphorylated-SMAD2/3, and phosphorylated-ERK1/2 during mouse incisor development

ABSTRACTBackground/aims: Connective tissue growth factor (CTGF) is a downstream mediator of transforming growth factor-beta 1 (TGF-β1) and TGF-β1-induced CTGF expression is regulated through SMAD and mitogen-activated protein kinase (MAPK) signaling pathways. However, little is known about the localization of CTGF and TGF-β1 signaling cascades during incisor development. Therefore, we aimed to investigate the distribution pattern of TGF-β1, CTGF, phosphorylated-SMAD2/3 (p-SMAD2/3), and phosphorylated-ERK1/2 (p-ERK1/2) in the developing mouse incisors.Materials and methods: ICR mice heads of embryonic (E) day 16.5, postnatal (PN) day 0.5 and PN3.5 were processed for immunohistochemistry.Results: From E16.5 to PN3.5, moderate to strong staining for TGF-β1 and CTGF was localized in stellate reticulum (SR), transit amplifying (TA) cells, outer enamel epithelium (OEE), preameloblasts (PA), preodontoblasts (PO), and dental papilla (DP). p-SMAD2/3 was weakly positive in SR and OEE at E16.5 and PN0.5 but was strongly positive in SR and OEE at PN3.5. Particularly, in the stem cell niche, p-SMAD2/3 was only localized in SR cells adjacent to OEE. There was no staining for p-SMAD2/3 in TA cells, PA and PO, although weak to moderate staining for p-SMAD2/3 was seen in DP. From E16.5 to PN3.5, p-ERK1/2 was negative in TA cells, OEE, PA and PO, whereas weak to moderate staining for p-ERK1/2 was observed in SR. DP was moderately stained for p-ERK1/2.Conclusions: TGF-β1 and CTGF show a similar expression, while p-SMAD2/3 and p-ERK1/2 exhibit differential distribution pattern, which indicates that CTGF and TGF-β1 signaling cascades might play a regulatory role in incisor development.

The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway

Trio, the Rho guanine nucleotide exchange factor (Rho-GEF), plays diverse roles in cell migration, cell axon guidance and cytoskeleton reorganization. Conserved during evolution, Trio encodes two guanine nucleotide exchange factor domains (GEFs) and activates small GTPases. The Rho-family small GTPases RhoA and Rac1, which are target molecules of Trio, have been described to engage in craniofacial development and tooth formation. However, the exact role of Trio in tooth development remains elusive. In this study, we generated Wnt1-cre;Triofl/fl mice to address the potential function of Trio in tooth development. Wnt1-cre;Triofl/fl mice showed short root deformity as well as decreased expression of odontogenic makers such as RUNX2, OSX, OCN, and OPN. In vitro, Trio was silenced in human stem cells of dental papilla (SCAPs). Compared with the control group, the proliferation and migration ability in the experimental group was disrupted. After knocking down Trio in SCAPs, the cells showed phenotypes of poor odontogenic differentiation and weak mineralized nodules. To study the underlying mechanism, we investigated the p38 MAPK pathway and found that loss of Trio blocked the cascade transduction of p38 MAPK signaling. In conclusion, we identified Trio as a novel coordinator in regulating root development and clarified its relevant molecular events.

Assessing the effect of triethyleneglycol dimethacrylate on tissue repair in 3D organotypic cultures.

Leachables from dental restoratives induce toxicity in gingival and pulp tissues and affect tissue regeneration/healing. Appropriate testing of these materials requires a platform that mimics the in vivo environment and allows the architectural self-assembly of cells into tissue constructs. In this study, we employ a new 3D model to assess the impact of triethyleneglycol dimethacrylate (TEGDMA) on early organization and advanced recruitment/accumulation of immortalized mouse gingival fibroblasts (GFs) and dental papilla mesenchymal cells (DPMCs) in extracellular matrix. We hypothesize that TEGDMA (1) interferes with the developmental architecture of GFs and DPMCs, and (2) inhibits the deposition of mineral. To test these hypotheses, GFs and DPMCs were incubated with the soluble TEGDMA at concentrations (0-2.5) mmol/L. Diameter and thickness of the constructs were determined by microscopic analysis. Cell differentiation was assessed by immunocytochemistry and the secreted mineral detected by alizarin-red staining. TEGDMA interfered with the development of GFs and/or DPMCs microtissues in a dose-dependent manner by inhibiting growth of inter-spherical cell layers and decreasing spheroid size (four to six times). At low/moderate TEGDMA levels, GFs organoids retained their structures while reducing thickness up to 21%. In contrast, at low TEGDMA doses, architecture of DPMC organoids was altered and thickness decreased almost twofold. Overall, developmental ability of TEGDMA-exposed GFs and DPMCs depended on TEGDMA level. GFs constructs were more resistant to structural modifications. The employed 3D platform was proven as an efficient tool for quantifying the effects of leachables on tissue repair capacities of gingiva and dental pulp.

Distribution of the neuropeptide calcitonin gene-related peptide-α of tooth germ during formation of the mouse mandible

Calcitonin gene-related peptide-α (CGRPα) is a neurotransmitter that is related to bone formation during development. However, CGRP expression is not well known to affect the formation of teeth during development. During tooth germ development, the relationships among CGRPα, calcitonin receptor-like receptor (CRLR), amelogenin (AMELX), dentin sialophosphoprotein (DSPP), osteopontin (OPN) and osteocalcin (OCN) are unclear despite various tooth and osteogenesis markers. Our real-time RT-PCR results showed that the expression levels of CGRPα mRNA gradually decreased, in contrast to the mRNA abundances of CRLR, AMELX, DSPP, OPN, and OCN, which rapidly increased from E14.5 to P1 in the mandible. In situ hybridization using an antisense probe for CGRPα mRNA showed significant localized expression levels around the tooth bud at E14.5 and epithelial cells near the dental ledge and outer and inner enamel epithelium at E17.5 compared to those at P1. The localization of the anti-CGRPα antibody reaction revealed a strong positive reaction at the surface layer of oral epithelial cells at E14.5 and oral epithelial cells of the dental lamina around the dental ledge depression in the mandible of E17.5 mice using immunohistochemical methods The different anti-CGRPα reaction revealed its important roles during tooth formation at the postnatal stage. CGRPα mRNA was also detected in the interactions of tooth germ with the formation of odontoblast and amelobast layers from dental papilla and inner enamel epithelium. CGRPα may also be related to tooth germ development. Furthermore, CGRPα is an important tooth and bone formation marker, and bone cells provide further evidence of a role in mandibular development in contrast to inflammatory systems.

DENS INVAGINATUS: REVISIÓN DE LITERATURA Y REPORTE DE 4 CASOS

OBJETIVO. Dens invaginatus también conocido como dens in dente es un trastorno del desarrollo que resulta de la invaginación del órgano del esmalte en la papila dental, comenzando en la corona y muchas veces extendiéndose hasta la raíz antes de que ocurra la calificación de la pieza dentaria. Afecta tanto a la dentición primaria como a la permanente. El incisivo lateral superior o maxilar es la pieza dentaria que se presenta afectada en mayor frecuencia. Debido a la presentación compleja y gran variación anatómica dificulta su diagnóstico. Hasta el día de hoy se utiliza la clasificación de Oehler. El objetivo de este artículo entregar una vista general sobre su etiopatogenia, frecuencia, categorización y aspectos clínicos y radiográficos, además de discutir cuatro casos de dens invaginatus.

Supernumerary Bilateral Tooth Germs Mimicking Radiolucent Bone Pathology

Immature tissues of tooth germs can mimic odontogenic and non-odontogenic lesions. This report is of a case of a 12-year-old Caucasian male patient, who attended a routine dental appointment. Periapical radiography revealed a circumscribed, unilocular, radiolucent area with a radiopaque halo between the right mandibular second premolar and the first molar. Because of the absence of signs, symptoms, and radiographic aspects, lateral periodontal cyst, odontogenic keratocyst, adenomatoid odontogenic tumor, unicystic ameloblastoma, and giant cell central lesion were included as differential diagnoses. Cone beam computed tomography showed a similar second image on the left mandibular side, between the second premolar and the first molar. Excisional biopsies and subsequent histopathologic findings of tissue fragments of tooth germs in the bell stage, with histo- and morpho-differentiation, comprising enamel organ and dental papilla, enabled the final diagnosis of tooth germs. Complete bone neoformation was observed, and after 2 years, the patient discontinued the follow-up.

Expression of ameloblastin in the human tooth germ and ameloblastoma.

To analyse the immunohistochemical expression of ameloblastin in the bell stage of tooth germ and compare with ameloblastoma to determine the level of differentiation of tumour cells. This study included eleven human tooth germs with four in the early and seven in the late bell stage, and six selected archival tissue samples of ameloblastomas were studied using haematoxylin and eosin, Masson's trichrome and ameloblastin. All eleven tooth germs reacted positively to ameloblastin with a characteristic inverted and sequential pattern of expression in the acellular zone of the dental papilla and enamel organ. Of the six cases of ameloblastoma, five cases showed a variable level of expression of ameloblastin in the tumour cells, whereas in one case, ameloblastin was negative in the tumour cells but positive in the stromal fibrous tissue collar. Expression of ameloblastin in human tooth germ is related to differentiation and mineralization, and it correlates with the state of differentiation of the tumour cells in ameloblastoma.

Microenvironmental Stiffness Regulates Dental Papilla Cell Differentiation: Implications for the Importance of Fibronectin-Paxillin-β-Catenin Axis.

The mechanical stiffness of substrates is recognized to be an important physical cue in the microenvironment of local cellular residents in mammalian species due to their great capacity in regulating cell behavior. Dental papilla cells (DPCs) play an important role in the field of dental tissue engineering for their stem cell-like properties. Therefore, it is essential to provide the suitable microenvironment by combining with the physical cues of biomaterials for DPCs to carry out the function of effective tissue regeneration. However, how the substrate stiffness influences the odontogenic differentiation of DPCs is still unclear. Thus, we fabricated poly(dimethylsiloxane) substrates with varied stiffness for cell behavior. Both cell morphology and focal adhesion were shown to have significant changes in response to varied stiffness. Paxillin, an important protein adapter of focal adhesion kinase protein, was shown to interact with both ectoplasmic fibronectin and cytoplasmic β-catenin by coimmunoprecipitation. The resultant changes of β-catenin by varied stiffness were confirmed by immunofluorescent stain and western blotting. Further, the higher quantity nuclear translocation of β-catenin and the less phospho-β-catenin on the stiff substrate were detected. This nuclear translocation in the stiff substrate finally led to an increased mineralization of DPCs relative to the soft substrate detected by Von Kossa and Alizarin Red stain. Taken together, this work not only points out that the substrate stiffness can regulate the odontogenic differentiation potential of DPCs via fibronectin/paxillin/β-catenin pathway but also provides significant consequence for biomechanical control of cell behavior in cell-based tooth tissue regeneration.

Overexpressed Sirt1 in MSCs Promotes Dentin Formation in Bmi1-Deficient Mice

Sirt1 promotes odontoblastic gene expression in human dental pulp cells, whereas the inhibition of Sirt1 downregulates the expression of those genes. To investigate whether the overexpression of Sirt1 in mesenchymal stem cells (MSCs) driven by Prx1 promoter could rescue the dentin formation defects in Bmi1-deficient (Bmi1−/−) mice, we established the MSCs overexpressing Sirt1 in Bmi1 knockout mice (Sirt1TGBmi1−/−). First, we used Prx1-Cre/ROSAnTnG mice to demonstrate that Prx1 linage cells exist mainly in the pulp horns at 4 wk of age. Second, we found that 4-wk-old Sirt1TG mice had increased tooth volume as compared with wild-type (WT) littermates. The expression level of Sirt1 was significantly higher in dental papilla mesenchymal cells of Sirt1TG mice than WT mice. Furthermore, we demonstrated that the tooth mineralization, dental volume, dentin sialoprotein–immunopositive areas, odontoblastic gene expression, and percentage of proliferating BrdU-positive cells were significantly elevated in the Sirt1TG mice and dramatically reduced in the Bmi1–/– mice versus the WT littermates at 4 wk of age. However, the areas of predentin and the percentage of TUNEL-positive apoptotic cells were significantly reduced in the Sirt1TG mice but dramatically increased in the Bmi1−/− mice as compared with the WT littermates. All these parameters were rescued in the Sirt1TGBmi1−/− mice versus the Bmi1−/− mice. Finally, by using dental papilla mesenchymal cells, we found that the overexpression of Sirt1 rescued the reduced cell proliferation and differentiation and increased the cell apoptosis caused by Bmi1 deficiency, which was associated with increased p53 deacetylation. Therefore, this study indicates that Sirt1 is a potential therapeutic target for promoting dentin formation in an anabolic approach to the treatment of dental developmental defects.

Strontium ranelate promotes odonto-/osteogenic differentiation/mineralization of dental papillae cells in vitro and mineralized tissue formation of the dental pulp in vivo

This study examined the effects and mechanisms of strontium ranelate (SrRn)—a drug used to treat osteoporosis—on the proliferation and differentiation/mineralization of cloned dental pulp-like cells (mouse dental papillae cells; MDPs). It also determined whether topical application of SrRn to exposed dental pulp tissue promotes the formation of mineralized tissue in vivo. The MDPs were cultured with or without SrRn, and cell proliferation, odonto-/osteoblastic gene expression, mineralized nodule formation, and Akt phosphorylation were evaluated. The formation of mineralized tissue in SrRn-treated pulp tissue in rat upper first molars was evaluated histologically. The SrRn up-regulated cell proliferation and expression of Alp (alkaline phosphatase), Bsp (bone sialoprotein), Dmp (dentin matrix acidic phosphoprotein)-1, Dspp (dentin sialophosphoprotein), and Oc (osteocalcin) in a dose-dependent manner. Mineralized nodule formation was also enhanced by SrRn. NPS-2143, a calcium-sensing receptor (CaSR) antagonist, and siRNA against the CaSR gene blocked SrRn-induced proliferation, odonto-/osteoblastic gene expression, and mineralized nodule formation. SrRn induced Akt phosphorylation, and this was blocked by NPS-2143. Topical application of SrRn to exposed rat molar pulps induced the formation of osteodentin-like mineralized tissue. Our study revealed for the first time that SrRn promotes proliferation and odonto-/osteogenic differentiation/mineralization of MDPs via PI3K/Akt signaling activated by CaSR in vitro; mineralized tissue forms from the dental pulp in vivo.

Case Report: A Primordial odontogenic tumor.

Introduction: Primordial odontogenic tumors are a rare recently described mixed odontogenic tumor composed histopathologically of dental papilla like tissue and enamel organ like tissue. Only nine cases have been documented worldwide and we are reporting the tenth case which is from Egypt. Clinical finding: A 2-year-old Egyptian boy that presented with an asymptomatic swelling of the mandible which appeared with multilocular radiolucency associated with an impacted developing tooth on a computerized tomography (CT) scan. Diagnoses, interventions, and outcomes: The lesion was excised and diagnosed as a primordial odontogenic tumor. The patient was followed up for two years with no recurrence. Conclusion: Differentiation of primordial odontogenic tumors from other odontogenic tumors, which resemble it histopathologically is crucial to avoid unnecessary aggressive treatment.

Inhibition of cell growth by cellular differentiation into adipocyte-like cells in dexamethasone sensitive cancer cell lines

ABSTRACTThe stress responses in human body lead to secretion of cortisol hormone. The present study investigated the cellular responses on cell growth and cellular differentiation into adipocytes by exposure of synthetic stress hormone, dexamethasone (DEX) in various human cancer and normal cells. After prolonged exposure of cells with 1 μg/ml DEX for 2 weeks, population doubling time (PDT) was significantly (P < .05) increased by inhibited cell growth in A-549 and MCF-7 cancer cells, and was unchanged in MDA-MB-231 cancer cells, normal MRC-5 fibroblasts, umbilical cord matrix-derived mesenchymal stem cells (UCMSCs) and dental papilla tissue-derived mesenchymal stem cells (DSCs). Whereas, PDT was significantly (P < .05) decreased in U87-MG cancer cells by increased cell growth. Glucose uptake was significantly (P < .05) increased in all the cancer cell lines compared to that in normal cell lines. Further, adiposome-like vesicles were noted in A-549 and MCF-7 cancer cells indicating retarded cell growth by DEX treatment, and the vesicles were stained with Oil-Red O solution. Further, the expression of adipocyte-specific genes such as glucose transporter type 4 (GLUT4), glucocorticoid receptors β (GRβ) and peroxisome proliferator-activated receptor γ (PPARγ) were significantly (P < .05) increased in A-549 and MCF-7 with lipid vesicles. The level of telomerase activity was found to be significantly (P < .05) downregulated in DEX-treated A-549 and MCF-7 cancer cells. Our results have clearly shown that DEX treatment induces inhibition of cell growth by differentiating into adipocyte-like cells in dexamethasone sensitive cancer cells.

Development of a novel biomaterial with an important osteoinductive capacity for hard tissue engineering.

In this study we designed a composite biomaterial based on a high viscosity soft propolis extract (70% propolis) and shell clam, with antiseptic and osteoinductive qualities, that can be used in dentistry, orthopedics and other areas where hard tissue regeneration is needed. We assessed it in interaction with stabilized human cells isolated from dental papilla of wisdom teeth (D1MSCs). We performed detailed characterization of the obtained material by Scanning Electronic Microscopy (SEM), X-Ray Diffraction (XRD), Energy Dispersive X-Ray Spectroscopy (EDX), Fourier Transform Infrared Spectroscopy (FTIR) techniques. SEM investigation revealed the roughness and porosity of the shell, which acted like a scaffold, as it allowed cells to penetrate the pores, proliferate on the surface, spread and grow in the depressions provided by the substrate. in vitro cell viability, proliferation and differentiation assays showed that the newly obtain biomaterial presented low toxicity on D1MSCs and determined the development of numerous osteogenic nodules that were in a higher number even than in the specific induction medium. Our results demonstrated that the shell-propolis based biomaterial promoted and sustained human stem cells attachment, proliferation and differentiation, presenting an important osteoinductive effect essential for mineralized tissue reparation process.

Expression of bone morphogenetic protein7 in developing rat tooth

Background: Bone morphogenetic proteins (BMPs) are secretory signal moleculeswhich have a variety of regulatory functions during morphogenesis and celldifferentiation. Teeth are typical examples of vertebrate organs in whichdevelopment is controlled by sequential and reciprocal signaling between theepithelium and mesenchyme. In addition, tooth development is characterized byformation of mineralized tissues, dentin and cementum as well as epitheliallyderived enamel. BMp 7 plays a role with other signaling molecules in toothdevelopment.Aim of the study: To perform immune-histochemical analysis of the expression ofBMP7starting from initiation of tooth development to completion of crownmorphogenesis when dentine and enamel matrices are being deposited in ratincisor tooth Materials and Methods: Sixteen rat embryos were obtained frompregnant rats in gestation periods 16th,17th,18th,20th intrauterine life and eightneonatal one day and 3 day old rat were included in this study . Each periodinvolved 4 embryos or neonatal rats. Premaxilla ( containing incisor teeth) wasdissected and fixed in 10% buffered formalin and embedded in paraffin. Blocksections (4 μm thickness) for Immunohistochemical localization of BMP7.Results: Positive expression of BMP7 was recorded in ectoderm derived cells only, indeveloping tooth germ include oral epithelia, dental lamina and inner enamelepithelia in gestation period 16th,17thand 18thintrauterin life of rat embryo. Thenthe expression was illustrated in specialized cell of dental papilla the odontoblastand the developing dentin matrix .Ameloblast cell expressed too BMP7 in itsformative and maturative stages.Conclusion: Bone morphogenetic protein 7 may play key roles in mediatinginduction, differentiation events during tooth development.

Primordial odontogenic tumor: Subepithelial expression of Syndecan-1 and Ki-67 suggests origin during early odontogenesis.

Primordial odontogenic tumor (POT) is composed of variably cellular myxoid connective tissue, surrounded by cuboidal to columnar odontogenic epithelium resembling the inner epithelium of the enamel organ, which often invaginates into the underlying connective tissue. The tumor is delimited at least partially by a thin fibrous capsule. It derives from the early stages of tooth development. Syndecan-1 is a heparan sulfate proteoglycan that has a physiological role in several cellular functions, including maintenance of the epithelial architecture, cell-to-cell adhesion and interaction of cells with extracellular matrix, and with diverse growth factors, stimulating cell proliferation. Ki-67 is considered the gold standard as a cell proliferation marker. The aim of this study was to examine the expression of Syndecan-1 and Ki-67 proliferation index in POT and normal tooth germs to better understand the biological behavior of this tumor. Results showed that Syndecan-1 was more intensely expressed in subepithelial mesenchymal areas of POT, in a pattern that resembles the early stages of tooth development. The cell proliferation index (4.1%) suggests that POT is a slow growing tumor. Syndecan-1 expression in tooth germs in late cap and early bell stages was similar to POT, showing immunopositivity in subepithelial mesenchymal condensed areas. The immunohistochemical findings showed a pattern in which the population of subepithelial mesenchymal cells exhibited greater proliferative activity than the central portion of the dental papilla.

Fascin in tooth germs: an immunohistochemical analysis

Development of a tooth is a complex process that involves three stages namely bud, cap and bell which results from the interaction of cells of oral mucosa and neural crest. During this process, oral and neural crest cells undergo various changes resulting in proliferation, apoptosis, morphological, and cyto-differentiation, which in turn would have changes in the cytoskeletal framework of the cell that includes actin and tubulin. Fascin is an actin-bundling protein that cross-links individual actin filaments into straight, compact, stiff bundles, which are crucial for the formation of finger-like membrane protrusions and aids in cell migration but is less explored in tooth germs. The aim of this study was analyze the expression and distribution of fascin in various stages of human tooth germs. Twenty human tooth germs were stained with hematoxylin and eosin and with immunohistochemical staining for fascin. Strong membranous expression for fascin was observed in various stages with decreased expression in stellate reticulum from cap stage to bell stage. Also, outer enamel epithelial cells had a weak fascin expression. Although cells of dental papilla did not express fascin in early cap stage of tooth development, strong expression of fascin was observed in later bell stages. It was also observed the inner enamel epithelium close to areas of calcification showed a decreased expression. Thus, the expression of fascin in various stages of tooth development being site and time specific may play an important role in cell remodulation.

Central odontogenic fibroma with unusual presenting symptoms

The central odontogenic fibroma is a rare benign odontogenic neoplasm. It arises from either dental follicle or periodontal ligament or dental papilla. The lesion is characterized by collagenous fibrous connective tissue, containing varying number of islands or strands of odontogenic epithelium. Here, we present a case report of odontogenic fibroma in a 20-year-old female patient with unusual presenting symptoms.