Loss of Bmp2 impairs odontogenesis via dysregulating pAkt/pErk/GCN5/Dlx3/Sp7.

BMP2 signaling plays a pivotal role in odontoblast differentiation and maturation during odontogenesis. Teeth lacking Bmp2 exhibit a morphology reminiscent of dentinogenesis imperfecta (DGI), associated with mutations in dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) genes. Mechanisms by which BMP2 signaling influences expressions of DSPP and DMP1 and contributes to DGI remain elusive.

Non-syndromic hypodontia of maxillary lateral incisors and its association with other dental anomalies.

Background: Tooth agenesis (TA) is the developmental absence of one or more teeth and is the most common craniofacial disorder in humans. Maxillary lateral incisor agenesis (MLIA) is a specific subtype of TA and can have esthetic, functional, and psychosocial implications for patients. The aim of this study was to evaluate the prevalence of MLIA amongst patients with non-syndromic tooth agenesis, as well as its association with other dental anomalies.

BMP Signaling Pathway in Dentin Development and Diseases.

BMP signaling plays an important role in dentin development. BMPs and antagonists regulate odontoblast differentiation and downstream gene expression via canonical Smad and non-canonical Smad signaling pathways. The interaction of BMPs with their receptors leads to the formation of complexes and the transduction of signals to the canonical Smad signaling pathway (for example, BMP ligands, receptors, and Smads) and the non-canonical Smad signaling pathway (for example, MAPKs, p38, Erk, JNK, and PI3K/Akt) to regulate dental mesenchymal stem cell/progenitor proliferation and differentiation during dentin development and homeostasis.

Fluoride Alters Signaling Pathways Associated with the Initiation of Dentin Mineralization in Enamel Fluorosis Susceptible Mice.

Fluoride can alter the formation of mineralized tissues, including enamel, dentin, and bone. Dentin fluorosis occurs in tandem with enamel fluorosis. However, the pathogenesis of dentin fluorosis and its mechanisms are poorly understood.

Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population.

Background: Undifferentiated pleomorphic sarcomas are one of the most common subtypes of soft tissue sarcomas. These are aggressive mesenchymal tumors and are devoid of the major known biomarkers except vimentin. Our objective was to establish and characterize a primary cell population from a mandibular UPS specimen.

Fluorescently Labeled Cetuximab-IRDye800 for Guided Surgical Excision of Ameloblastoma: A Proof of Principle Study.

Purpose: Fluorescently labeled epidermal growth factor receptor (EGFR) antibodies have successfully identified microscopic tumors in multiple in vivo models of human cancers with limited toxicity. The present study sought to demonstrate the ability of fluorescently labeled anti-EGFR, cetuximab-IRDye800, to localize to ameloblastoma (AB) tumor cells in vitro and in vivo.

Material And Methods: EGFR expression in AB cells was confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry.

Establishment and characterization of immortalized mouse ameloblast-like cell lines.

Objectives: Enamel organ epithelium (EOE) gives rise to the major epithelial-derived cell types of tooth including the ameloblasts. The formation of enamel, termed amelogenesis, occurs through the cytodifferentiation of ameloblasts, ultimately leading to apoptosis and necrosis of these cells with eruption. Therefore, studies regarding enamel matrix formation and bioengineering have been limited.

Should the U.S. Adopt a National Dental Clinical Licensure Examination? Two Viewpoints: Viewpoint 1: National Licensure Would Provide Multiple Advantages for Practitioners and the Profession and Viewpoint 2: Licensing Authority Should Remain Under State Dental Boards' Jurisdiction.

This Point/Counterpoint article examines the need for and potential impact of implementing a national clinical examination for initial licensure in dentistry. Viewpoint 1 supports a national licensure exam that meets the clinical exam's credentialing requirement for licensure in every state. According to this viewpoint, a national exam will reduce costs, enhance portability of graduates, simplify the transition from dental school to practice or specialty training programs, and standardize requirements for licensure between states.

Ethnic differences in the root to crown ratios of the permanent dentition.

Objective: Root resorption due to orthodontic tooth movement may adversely affect the root-crown (R/C) ratios of permanent teeth, especially in patients with Short Root Anomaly (SRA), a poorly understood disorder affecting root development. Evaluation of SRA R/C ratios to normal dentition would facilitate diagnosis and orthodontic treatment planning. However, reference values are not available for all ethnicities.

Gene-Expression Analysis Identifies IGFBP2 Dysregulation in Dental Pulp Cells From Human Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder affecting osteoblast differentiation, chondrocyte maturation, skeletal morphogenesis, and tooth formation. Dental phenotype in CCD include over-retained primary teeth, failed eruption of permanent teeth, and supernumerary teeth. The underlying mechanism is unclear.

Loss of Stemness, EMT, and Supernumerary Tooth Formation in CebpbRunx2 Murine Incisors.

Adult Cebpb KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, Cebpb acts upstream of Sox2 to regulate stemness. In this study, Cebpb KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a Cebpb knockdown mouse enamel epithelial stem cell line.

Surgical Management and Evaluation of the Craniofacial Growth and Morphology in Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD, MIM 119600) is a rare autosomal dominant disorder affecting bone, cartilage, craniofacial growth, and tooth formation leading to supernumerary teeth. Few reports delineate the genotype-phenotype correlations related to the variations in craniofacial morphology and patterning of the dentition and the complexity of treating patient's malocclusion. Successful management of the craniofacial deformities in patients with CCD requires a multidisciplinary team of healthcare specialists.

RIG-I-Like Receptor Signaling in Singleton-Merten Syndrome.

Singleton-Merten syndrome (SMS) is an autosomal dominant, multi-system innate immune disorder characterized by early and severe aortic and valvular calcification, dental and skeletal abnormalities, psoriasis, glaucoma, and other varying clinical findings. Recently we identified a specific gain-of-function mutation in , interferon induced with helicase C domain 1, segregated with this disease. SMS disease without hallmark dental anomalies, termed atypical SMS, has recently been reported caused by variants in , DEXD/H-box helicase 58.

BMP-2 induced Dspp transcription is mediated by Dlx3/Osx signaling pathway in odontoblasts.

Dentin sialophosphoprotein (Dspp) as a differentiation marker of odontoblasts is regulated by BMP-2. However, the intimate mechanism is still unknown. Transcription factors Dlx3 and Osx are essential for odontoblasts differentiation.

Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation.

Dentin sialoprotein (DSP) is a dentin extracellular matrix protein. It is involved in dental mesenchymal cell lineages and dentin formation through regulation of its target gene expression. DSP mutations cause dentin genetic diseases.

Dentin Sialoprotein is a Novel Substrate of Matrix Metalloproteinase 9 in vitro and in vivo.

Dentin sialoprotein (DSP) is essential for dentinogenesis and processed into fragments in the odontoblast-like cells and the tooth compartments. Matrix metalloproteinase 9 (MMP9) is expressed in teeth from early embryonic to adult stage. Although MMP9 has been reported to be involved in some physiological and pathological conditions through processing substrates, its role in tooth development and whether DSP is a substrate of MMP9 remain unknown.

Molecular Signaling in Benign Odontogenic Neoplasia Pathogenesis.

Several molecular pathways have been shown to play critical roles in the pathogenesis of odontogenic tumors. These neoplasms arise from the epithelial or mesenchymal cells of the dental apparatus in the jaw or oral mucosa. Next generation genomic sequencing has identified gene mutations or single nucleotide polymorphisms associated with many of these tumors.

Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development.

Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors.

MEPE Localization in the Craniofacial Complex and Function in Tooth Dentin Formation.

Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein found in dental and skeletal tissues. Although information regarding the role of MEPE in bone and disorders of phosphate metabolism is emerging, the role of MEPE in dental tissues remains unclear. We performed RNA in situ hybridization and immunohistochemistry analyses to delineate the expression pattern of MEPE during embryonic and postnatal development in craniofacial mineralizing tissues.

NFI-C2 temporal-spatial expression and cellular localization pattern during tooth formation.

Currently, little is known regarding critical signaling pathways during later stages of tooth development, especially those associated with root formation. Nfi-c null mice, lacking molar roots, have implicated the transcription factor NFI-C as having an essential role in root development. Previously, we identified three NFI-C isoforms expressed in dental tissues with NFI-C2 being the major transcript.

Effects of FGFR Signaling on Cell Proliferation and Differentiation of Apert Dental Cells.

The Apert syndrome is a rare congenital disorder most often arising from S252W or P253R mutations in fibroblast growth factor receptor (FGFR2). Numerous studies have focused on the regulatory role of Apert FGFR2 signaling in bone formation, whereas its functional role in tooth development is largely unknown. To investigate the role of FGFR signaling in cell proliferation and odontogenic differentiation of human dental cells in vitro, we isolated dental pulp and enamel organ epithelia (EOE) tissues from an Apert patient carrying the S252W FGFR2 mutation.

Establishment of Immortalized BMP2/4 Double Knock-Out Osteoblastic Cells Is Essential for Study of Osteoblast Growth, Differentiation, and Osteogenesis.

Bone morphogenetic proteins 2 and 4 (BMP2/4) are essential for osteoblast differentiation and osteogenesis. Generation of a BMP2/4 dual knock-out ((ko/ko)) osteoblastic cell line is a valuable asset for studying effects of BMP2/4 on skeletal development. In this study, our goal was to create immortalized mouse deleted BMP2/4 osteoblasts by infecting adenoviruses with Cre recombinase and green fluorescent protein genes into immortalized murine floxed BMP2/4 osteoblasts.

Reduced Dentin Matrix Protein Expression in Camurati-Engelmann Disease Transgenic Mouse Model.

Unlabelled: Overexpression of transforming growth factor-β1 (TGF-β1) has been shown to lead to mineralization defects in both the enamel and dentin layers of teeth. A TGFB1 point mutation (H222D), derived from published cases of Camurati-Engelmann disease (CED), has been shown to constitutively activate TGF-β1, leading to excess bone matrix production. Although CED has been well documented in clinical case reports, there are no published studies on the effect of CED on the dentition.