Radiological features and treatment of erupting maxillary canines in relation to the occurrence of dental developmental abnormalities.

OBJECTIVE: This study aimed to investigate the radiological features of the permanent canines and the treatment carried out to ensure their eruption relative to certain features involved in Dental Anomaly Patterns (DAP). MATERIAL AND METHODS: The cross-sectional part of this retrospective register--based study focused on 1,315 dental panoramic tomographs (DPTs) of children aged 8.5-10.5 years, while the longitudinal part involved information on the treatment provided for 1,269 canines after the DPTs and on their eruption into the oral cavity. RESULTS: The canines of the DAP children more often showed evidence of early treatment (p = 0.014), with girls having more frequently interceptive treatment (p = 0.004) and boys early headgear (p = 0.022). Delayed dental age was associated with early treatment (OR 3.29, 95% CI 1.08-9.99). Either no or clear overlapping of a canine with the lateral incisor occurred more often in the DAP children, whereas canine inclination did not differ between the groups. The root development stage of the canine was more often either beginning or well advanced in the DAP children. CONCLUSIONS: The children with dental developmental abnormalities more often showed evidence of early treatment for the canines. Monitoring of the erupting canines after the first mixed stage is important to enable timely early treatment.

Developmental characteristics of the permanent upper lateral incisor in unilateral cleft lip and palate.

OBJECTIVES: This study aims to provide insights into the developmental characteristics of the upper lateral incisor in individuals with unilateral clefts. MATERIALS AND METHODS: Panoramic radiographs of a consistent group of Caucasian children taken over time (ages 6, 9, and 12) were extensively reviewed. The study assessed the distribution pattern, eruption path, tooth development, and crown size of the upper lateral incisor within the cleft region. RESULTS: The most commonly observed distribution pattern was the lateral incisor located distal to the cleft, accounting for 49.2% of cases. Furthermore, a significant delay in tooth development of the upper lateral incisor on the cleft side was noted at ages 6 and 9 (p > 0.001). Compared with the non-cleft side, these incisors often erupted along the alveolar cleft and exhibited microdontia (88.3%, p < 0.041). CONCLUSION: Lateral incisors on the cleft side display unique distribution patterns, microdontia, and delayed tooth development. Careful monitoring of the cuspid eruption is essential, as it can influence the eruption of the lateral incisor. CLINICAL RELEVANCE: A comprehensive understanding of the development of the upper lateral incisor relative to the cleft is vital for determining its prognosis over time. The position of the upper lateral incisor can also influence the timing and prognosis of secondary alveolar bone grafting. Preserving the upper lateral incisor favors arch length, perimeter, and symmetry in individuals with unilateral clefts.

Evaluation of tooth eruption rate of incisor teeth in rats with estrogen deficiency.

OBJECTIVES: To assess the influence of estrogen deficiency on tooth eruption rate (TER) and gene expression of estrogen receptor alpha and beta (ERα and ERß) in the odontogenic region of teeth with continuous formation in a rat model. MATERIALS AND METHODS: Ovariectomies (OVX; n = 25) and sham surgeries (SHAM; n = 25) were performed in female Wistar rats when animals were 25 days old. The TER of the lower incisors, both in impeded (hyperfunction condition) and unimpeded (trimmed incisal edge-hypofunction condition) conditions, was evaluated using standardized digital photographs acquired every 48-72 h for 3 weeks (35th-53rd day of life), using a camera coupled to a stereomicroscope. Quantitative real-time PCR was performed to evaluate the relative gene expression of ERα and ERß in the odontogenic region. RESULTS: The OVX group showed a significant reduction in TER when compared to the SHAM group, only in the impeded condition (p = 0.03). There was no statistically significant difference between the groups in ERα gene expression (p = 0.33). ERß showed a significantly higher gene expression in the OVX group (p ≤ 0.05). CONCLUSIONS: Estrogen deficiency decreases TER in teeth under impeded condition. Estrogen deficiency also increases ERß gene expression in the odontogenic region of teeth with continuous formation. CLINICAL RELEVANCE: Hormonal disturbances affecting estrogen levels can cause alterations in dental formation and teeth eruption.

Multiple roles of Runt-related transcription factor-2 in tooth eruption: bone formation and resorption.

OBJECTIVE: The aim was to provide a comprehensive review of the current knowledge of the multiple roles of Runt-related transcription factor-2 (RUNX2) in regulating tooth eruption, focusing on the molecular mechanisms regarding tooth eruption mediated by RUNX2. DESIGN: Relevant literatures in PubMed, Medline, and Scopus database were searched, and a narrative review was performed. The multiple roles of RUNX2 in regulating tooth eruption was reviewed and discussed. RESULTS: Aberrant RUNX2 expression leads to disturbed or failed tooth eruption. Tooth eruption involves both the process of bone formation and bone resorption. RUNX2 promotes osteogenesis around the radicular portion of the dental follicle that provides the biological force for tooth eruption through inducing the expression of osteogenesis-related genes in dental follicle cells/osteoblasts. On the other hand, through indirect and direct pathways, RUNX2 regulates osteoclastogenesis and the formation of the eruption pathway. CONCLUSION: RUNX2 exerts a pivotal and complex influence in regulating tooth eruption. This review provides a better understanding of the function of RUNX2 in tooth eruption, which is beneficial to illuminate the precise molecular mechanism of osteogenesis and bone resorption, aiding the development of effective therapy for the failure of tooth eruption.

Odontomas: un reto para el tratamiento interdisciplinario del paciente de ortodoncia / Odontomas: a challenge for the interdisciplinary treatment of the orthodontic patient

El objetivo del presente trabajo es describir las técnicas para el diagnóstico y tratamiento de 3 casos clínicos de odontoma en pacientes ortodóncicos. En el caso 1, se trató a un paciente masculino de 17 años, que acudió para interconsulta con el servicio de ortodoncia, ya que no había erupcionado el canino superior izquierdo y el primer premolar superior izquierdo. El estudio anatomopatológico reveló odontoma complejo con áreas pindborgoides y acumulación de células fantasma. En al caso 2 se trató a un paciente femenino de 15 años. El estudio anatomopatológico reveló odontoma complejo. En el caso 3, se trató a un paciente masculino de 28 años que acudió a rehabilitación integral de su boca, y fue derivado a la cátedra de ortodoncia. En la radiografía panorámica se observó una imagen compatible con odontoma. Se remitió una muestra a anatomía patológica que confirmó el diagnóstico de odontoma. Conclusión: el conocimiento adecuado de las características clínicas, radiológicas y patológicas es necesario para un correcto diagnóstico y tratamiento. Es importante el trabajo interdisciplinario ortodoncista - cirujano para tratar estos casos (AU)

The objective of this work is to describe the techniques for the diagnosis and treatment of 3 clinical cases of odontoma in orthodontic patients. In case 1, a 17-year-old male patient was treated who came for consultation with the orthodontic service, since the upper left canine and the upper left first premolar had not erupted. Pathological study revealed complex odontoma with pindborgoid areas and accumulation of ghost cells. In case 2, a 15-year-old female patient was treated. The anatomopathological study revealed a complex odontoma. In case 3, a 28-year-old male patient was treated who attended comprehensive rehabilitation of his mouth and was referred to the orthodontic department. In the panoramic radiography, an image compatible with odontoma was observed. A sample was sent to pathological anatomy, which confirmed the diagnosis of odontoma. Conclusion: Adequate knowledge of the clinical, radiological and pathological characteristics is necessary for a correct diagnosis and treatment. Interdisciplinary orthodontist-surgeon work is important to treat these cases (AU)

Application of cryopreservation to tooth germ transplantation for root development and tooth eruption.

We cryopreserved mouse tooth germs with widely open cervical margins of the enamel organ to overcome difficulties in cryoprotectant permeation and tested their efficacy by transplanting them into recipient mice. The upper right first molar germs of 8-day-old donor mice were extracted and categorized into the following four groups according to cryopreservation time: no cryopreservation, 1 week, 1 month, and 3 months. The donor tooth germs were transplanted into the upper right first molar germ sockets of the 8-day-old recipient mice. The upper left first molars of the recipient mice were used as controls. The outcome of the transplantation was assessed at 1, 2, and 3 weeks after transplantation. Stereomicroscopic evaluation revealed that most of the transplanted teeth erupted by 3 weeks after transplantation. Micro-computed tomography analysis revealed root elongation in the transplanted groups as well as in the controls. There was no significant difference between the cryopreserved and non-cryopreserved transplanted teeth, but the roots of the cryopreserved teeth were significantly shorter than those of the control teeth. Histological examination revealed root and periodontal ligament formations in all the transplanted groups. These results suggest that the transplantation of cryopreserved tooth germs facilitates subsequent root elongation and tooth eruption.

New cladotherian mammal from southern Chile and the evolution of mesungulatid meridiolestidans at the dusk of the Mesozoic era.

In the last decades, several discoveries have uncovered the complexity of mammalian evolution during the Mesozoic Era, including important Gondwanan lineages: the australosphenidans, gondwanatherians, and meridiolestidans (Dryolestoidea). Most often, their presence and diversity is documented by isolated teeth and jaws. Here, we describe a new meridiolestidan mammal, Orretherium tzen gen. et sp. nov., from the Late Cretaceous of southern Chile, based on a partial jaw with five cheek teeth in locis and an isolated upper premolar. Phylogenetic analysis places Orretherium as the earliest divergence within Mesungulatidae, before other forms such as the Late Cretaceous Mesungulatum and Coloniatherium, and the early Paleocene Peligrotherium. The in loco tooth sequence (last two premolars and three molars) is the first recovered for a Cretaceous taxon in this family and suggests that reconstructed tooth sequences for other Mesozoic mesungulatids may include more than one species. Tooth eruption and replacement show that molar eruption in mesungulatids is heterochronically delayed with regard to basal dryolestoids, with therian-like simultaneous eruption of the last premolar and last molar. Meridiolestidans seem endemic to Patagonia, but given their diversity and abundance, and the similarity of vertebrate faunas in other regions of Gondwana, they may yet be discovered in other continents.

Miniaturization: How many cells are needed to build a tooth?

BACKGROUND: Organs that develop early in life, and are replaced by a larger version as the animal grows, often represent a miniature version of the adult organ. Teeth constituting the first functional dentition in small-sized teleost fish, such as medaka (Oryzias latipes), are examples of such miniature organs. With a dentin cone as small as the size of one human cell, or even smaller, these teeth raise the question how many dentin-producing cells (odontoblasts) are required to build such a tooth, and whether this number can be as little as one. RESULTS: Based on detailed observations with transmission electron microscopy (TEM) and TEM-based 3D-reconstructions, we show that only one mesenchymal cell qualifies as a true odontoblast. A second mesenchymal cell potentially participates in dentin formation, but only at a late stage of tooth development. Moreover, the fate of these cells appears to be specified very early during tooth development. CONCLUSIONS: Our observations indicate that in this system, one single odontoblast fulfills roles normally exerted by a large and communicating cell population. First-generation teeth in medaka thus provide an exciting model to study integration of multiple functions into a single cell.

Impactación Canina Maxilar y Reabsorción Radicular de Dientes Adyacentes: Un Análisis a Través de Tomografía Computarizada Cone-Beam / Canine Maxillary Impaction and Root Resorption of Adjacent Teeth: An Analysis through Cone-Beam Computed Tomography Analysis

RESUMEN: Uno de los problemas con mayores consecuencias tanto estéticas como funcionales en ortodoncia es la impactación de caninos maxilares (ICM) siendo principal motivo de reabsorciones radiculares de dientes adyacentes. Actualmente se carece de estudios que describan la reabsorción radicular por ICM a través de tomografía computarizada conebeam (TCCB) en la población chilena. El objetivo del estudio fue describir a pacientes entre 8 a 18 años, que presentan ICM (o riesgo de ella), tanto en las características de la impactación canina como en la reabsorción radicular presentada en incisivos laterales (IL) y en otros dientes adyacentes. En este estudio retrospectivo, 135 datos de TCCB fueron seleccionados por conveniencia, de los cuales 181 caninos presentaron ICM. Fueron analizadas las variables edad, sexo, tipo de ICM (unilateral o bilateral), localización bucolingual (vestibular o palatino), lado de impactación (derecho o izquierdo), reabsorción radicular en el incisivo lateral y registro de el o los dientes anexos afectados por reabsorción radicular (incisivo central y/o premolares). Además en el caso de reabsorción de IL fue analizada la reabsorción tridimensionalmente a través de la ThreeDimensional Leeds Orthodontic Root Resorption Target Scale (3D-LORTS). La ICM en la muestra seleccionada tuvo una edad promedio de 12 años, una relación por sexo mujeres:hombres de 1,5:1, frecuentemente de tipo unilateral, en el lado derecho y una localización bucolingual palatina (64,1 %) por sobre la vestibular (35,9 %). La reabsorción radicular alcanzó un 35,9 %, de la cual un 27,6 % involucró a IL y un 8,3 % en dientes anexos adyacentes. En cuanto a la distribución tridimensional de la reabsorción radicular, la más frecuente involucró el tercio apical (60 %), con compromiso pulpar o severo (40 %), involucrando solo una cara, la palatina (54 %). Ninguna de las variables anteriores consideradas, demostró diferencias estadísticas con la reabsorción radicular de incisivos laterales.

ABSTRACT: One of the problems with greatest aesthetic and functional consequences in orthodontics is the Impaction of Maxillary Canines (ICM) being the main reason for root resorption of the adjacent teeth. Currently there are no studies describing root resorption by ICM through cone beam computed tomography (CBCT) in the Chilean population. The main objective of the study was to describe patients between 8 and 18 years old, who presented with ICM (or risk thereof), with the characteristics of canine impaction as well as root resorption presented in lateral incisors (IL) and in other adjacent teeth. In this retrospective study, 135 CBCT subjects were selected for convenience, of which 181 canines presented ICM. The variables were analyzed: age, sex, type of ICM (unilateral or bilateral), buccolingual location (vestibular or palatal), side of impaction (right or left), root resorption in the lateral incisor and registration of adjacent teeth affected by resorption radicular (central incisor and/or premolars). In addition, when reabsorption of IL was observed, three-dimensional analysis was made using the Three-Dimensional Leeds Orthodontic Root Resorption Target Scale (3D-LORTS). The ICM in the selected sample had an average age of 12 years, a ratio by sex of women:men of 1.5:1, frequently of unilateral type, on the right side and with palatine buccolingual location (64.1 %) above the vestibular (35.9 %). Root resorption reached 35.9 %, of which 27.6 % presented in the IL and 8.3 % in adjacent teeth. Regarding the three-dimensional distribution of root resorption, the most frequent involved the apical third (60 %), with pulpal or severe damage (40 %), in only one location, the palatine (54 %). None of the above variables considered showed statistical differences with the root resorption of lateral incisors.

Developmental variability channels mouse molar evolution.

Do developmental systems preferentially produce certain types of variation that orient phenotypic evolution along preferred directions? At different scales, from the intra-population to the interspecific, the murine first upper molar shows repeated anterior elongation. Using a novel quantitative approach to compare the development of two mouse strains with short or long molars, we identified temporal, spatial and functional differences in tooth signaling center activity, that arise from differential tuning of the activation-inhibition mechanisms underlying tooth patterning. By tracing their fate, we could explain why only the upper first molar reacts via elongation of its anterior part. Despite a lack of genetic variation, individuals of the elongated strain varied in tooth length and the temporal dynamics of their signaling centers, highlighting the intrinsic instability of the upper molar developmental system. Collectively, these results reveal the variational properties of murine molar development that drive morphological evolution along a line of least resistance.

Over time species develop random mutations in their genetic sequence that causes their form to change. If this new form increases the survival of a species it will become favored through natural selection and is more likely to get passed on to future generations. But, the evolution of these new traits also depends on what happens during development. Developmental mechanisms control how an embryo progresses from a single cell to an adult organism made of many cells. Mutations that alter these processes can influence the physical outcome of development, and cause a new trait to form. This means that if many different mutations alter development in a similar way, this can lead to the same physical change, making it 'easy' for a new trait to repeatedly occur. Most of the research has focused on finding the mutations that underlie repeated evolution, but rarely on identifying the role of the underlying developmental mechanisms. To bridge this gap, Hayden et al. investigated how changes during development influence the shape and size of molar teeth in mice. In some wild species of mice, the front part of the first upper molar is longer than in other species. This elongation, which is repeatedly found in mice from different islands, likely came from developmental mechanisms. Tooth development in mice has been well-studied in the laboratory, and Hayden et al. started by identifying two strains of laboratory mice that mimic the teeth seen in their wild cousins, one with elongated upper first molars and another with short ones. Comparing how these two strains of mice developed their elongated or short teeth revealed key differences in the embryonic structures that form the upper molar and cause it to elongate. Further work showed that variations in these embryonic structures can even cause mice that are genetically identical to have longer or shorter upper first molars. These findings show how early differences during development can lead to small variations in form between adult species of mice. This study highlights how studying developmental differences as well as genetic sequences can further our understanding of how different species evolved.

Analysis of Estrogen Effects on Eruption of Rat Molars / Análisis de los Efectos del Estrógeno en la Erupción de Molares de Rata

ABSTRACT: Tooth eruption requires resorption of the alveolar bone interposed between the tooth germ and the oral mucosa (coronal bone). The cells responsible for bone resorption are the osteoclasts and their activity can be reduced or inactivated by estrogen hormone. We aimed to investigate the effects of estrogen on the process of tooth eruption in rats. Thirty-three Wistar rats, aged two-to-17-days, were divided into control, sham and estrogen-treated groups. After daily injections with estrogen, the animals were euthanized and the jaws removed and processed for histological analysis. We performed clinical examination, morphological analysis, quantification of the number of osteoclasts on the surface of the coronal bone and immunohistochemical analysis of estrogen receptor type alpha (ERα). Estrogen therapy was effective, which could be confirmed by the higher estrogen plasma levels on treated animals. However, it had no effect on tooth development or tooth eruption. Progressive bone resorption was observed and the number of osteoclasts on coronal bone was not affected on hormoneinjected animals, allowing tooth to erupt at the same time observed in untreated animals. Immunohistochemistry for ERα confirmed the presence of this type of receptor in osteoclasts, osteoblasts and osteocytes. Taken together, our results showed that estrogen stimulation was not sufficient to decrease the number of osteoclasts on the coronal bone, supporting the idea that, although estrogen may have a protective activity on bone resorption, this may not apply to the alveolar bone that is meant to be resorbed during eruptive process.

RESUMEN: La erupción dental requiere la resorción del hueso alveolar interpuesto entre el germen dental y la mucosa oral (hueso coronal). Las células responsables de la resorción ósea son los osteoclastos y su actividad puede reducirse o inactivarse por la hormona del estrógeno. Objetivos: apuntamos a investigar los efectos del estrógeno en el proceso de la erupción dental en ratas. Treinta y tres ratas Wistar, de dos a 17 días de edad, se dividieron en grupos de control, Sham y se trataron con estrógenos. Los animales fueron eutanizados después del tratamento con estrógeno y se procesaron las mandíbulas para el análisis histológico. Se realizó el examen clínico, el análisis morfológico, la cuantificación del número de osteoclastos en la superficie del hueso coronal y el análisis inmunohistoquímico del tipo de receptor de estrógeno alfa (ERα). La terapia de estrógeno fue eficaz, lo que podría ser confirmado por los niveles plasmáticos más altos de estrógeno en los animales tratados. Sin embargo, no se observó ningún efecto sobre el desarrollo de los dientes o la erupción dental. Se observó una resorción ósea progresiva y el número de osteoclastos en el hueso coronal no se vio afectado en los animales inyectados con hormonas, permitiendo que el diente erupcionó durante el mismo período de tiempo observado en animales no tratados. La inmunohistoquímica para el ERα confirmó la presencia de este tipo de receptor en los osteoclastos, osteoblastos y osteocitos. Nuestros resultados mostraron que la estimulación del estrógeno no fue suficiente para reducir el número de osteoclastos en el hueso coronal confirmando que, si bien el estrógeno puede tener una actividad protectora en la resorción ósea, esto puede no se aplica al hueso alveolar que está destinado a ser rerecurrido durante el proceso eruptivo.

Semaphorin 3A gets involved in the establishment of mouse tooth eruptive pathway.

The accurately establishment of the eruptive pathway is of vital importance. The mechanisms governing tooth eruption pathway remain little known. This study is to elucidate the roles of Semaphorin 3A (Sema 3A) in mouse tooth eruptive pathway. C57BL/6 mice (11-13 and 15-17 days after birth) were chosen to observe eruptive pathway of mouse lower first molar. Expressions of Sema 3A and its receptor neuropilin 1 and plexin A1 were detected. Osteoclasts were identified by TRAP staining. Co-localization of Sema 3A and osteoclast maker CD68 was detected by double immunofluorescence staining. Picrosirius red staining was applied to observe collagen fibers during mucosal penetration phase. In vitro, Bone marrow-derived macrophages (BMMs) were prepared from 4 week C57BL/6 mice to observe the effect of Sema 3A on the differentiation of BMMs into osteoclasts by TRAP staining. Expressions of Sema 3A was observed by immunofluorescence and western blotting. At osseous eruption phase, many TRAP-positive multi-nucleated cells were distributed around occlusal alveolar bone. The positive expressions of Sema 3A were observed in the multi-nucleated cells. Fluorescence double staining showed that Sema 3A and CD68 were co-expressed in osteoclasts. Its receptor neuropilin 1 and plexin A1 were also found in osteoclasts. In vitro, Sema3A negatively regulated osteoclast differentiation. At mucosal penetration, occlusal alveolar bone had been completely resorbed and collagen fires were gradually degraded for eruptive pathway. Similar positive expressions of Sema 3A and its receptor neuropilin 1 and plexin A1 were also found in the mucosal penetration pathway. Sema 3A gets involved in the establishment of mouse tooth eruptive pathway by modulating osteoclast activity. Sema3A should be considered as a novel nervous agent or a potential biomarker for mouse tooth eruptive pathway.

Dental development in cleft lip and palate patients: A systematic review.

OBJECTIVE: To investigate a potential delay in dental development in cleft patients compared with non-cleft patients. SEARCH METHODS: An unlimited electronic search was performed in four databases (PubMed, Embase, Lilacs and OpenGrey), from inception until October 2018. Full text articles concerning dental development or tooth eruption of non-syndromic children with cleft lip and/or palate (CL(P)) were included and reviewed. Case reports/series, review articles, articles in languages other than English, Dutch, French or Spanish and studies considering the eruption of deciduous teeth were excluded. Data extraction followed the PRISMA guidelines and study quality was assessed using MINORS. RESULTS: The primary search resulted in 991 citations, of which 36 studies were finally analyzed. Most articles were retrospective studies based on panoramic radiographs. A delay in tooth development or -eruption in CL(P) patients was found in 32 out of the 36 included articles. The amount of delay varied from 0.20 to 0.90 years, with a mean delay of 0.56 years for all types of clefts. In UCLP patients, a mean delay of 0.53 years was found. The lateral incisor at the cleft side was generally the most delayed. Conflicting results were found regarding the influence of sex and age. The amount of delay was reported to be independent of the cleft severity or type. The teeth near the cleft generally showed a greater delay than the teeth further away from it. Finally, an increased risk of asymmetrical tooth development in CL(P) patients was observed in all publications studying this aspect. 31 articles were comparative, 5 were non-comparative; with a median MINORS score of 16/24 (range 10-18) and 10/16 (range 8-10) for both groups respectively. CONCLUSIONS: The majority of the included articles reports a delay in dental development or tooth eruption in CL(P) patients compared to non-CL(P) patients. The obtained results could be important for forensic age estimation outcomes and for orthodontic and surgical treatment planning in CL(P) patients. The delay in tooth development implies a delay in start of orthodontic treatment. Moreover, CL(P) patients could falsely be considered to be a minor when applying the existing reference tables for dental age estimation. SYSTEMATIC REVIEW REGISTRATION: International prospective register of systematic reviews (PROSPERO: CRD42018082106).

Clinical and x-ray oral evaluation in patients with congenital Zika Virus.

OBJECTIVE: The aim of this study was to investigate possible malformations in the soft, bone and/or dental tissues in patients with congenital Zika Virus (ZIKV) by clinical and x-ray evaluation. METHODOLOGY: Thirty children born with ZIKV and 30 children born without ZIKV (control group) were included in the study. Patients were evaluated over 24 consecutive months according to the variables: sex, age, cleft palates, soft tissue lesions, alveolar ridge hyperplasia, short labial and lingual frenums, inadequate posture of the lingual and perioral muscles at rest, micrognathia, narrow palatine vaults, changes in the teeth shape and/or number, sequence eruption, spasms, seizures and eruption delay were evaluated. Chi-square test, Student's t-test and nominal logistic regression were used (p<0.05). RESULTS: Among the 30 babies examined, the mean age of the first dental eruption was 10.8±3.8 with almost two-thirds of the children (n=18, 60%) experiencing eruptions of their first tooth after 9 months of age, nine children (30%) had inadequate lingual posture at rest, more than half of the children (n=18, 60%) had short labial or lingual frenums. ZIKV babies showed a high prevalence of clef palate (p<0.001), inadequate lingual posture at rest (p=0.004), micrognathia (p=0.002), changes in the shape and/or number of teeth (p=0.006), alteration in sequence of dental eruption (p<0.001) and muscles spasms (p=0.002). The delay eruption was associated with inadequate lingual posture at rest (p=0.047), micrognathia (p=0.002) and changes in the shape and/or number of teeth (p=0.021). The delayed eruption (p=0.006) and narrow palatine vaults (p=0.008) were independently associated with ZIKV. Moreover, female patients showed the most narrow palatine vaults (p=0.010). CONCLUSIONS: The children with ZIKV showed a greater tendency to have delayed eruption of the first deciduous tooth, inadequate lingual posture and short labial and lingual frenums.

Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption.

Formation of functional skeletal tissues requires highly organized steps of mesenchymal progenitor cell differentiation. The dental follicle (DF) surrounding the developing tooth harbors mesenchymal progenitor cells for various differentiated cells constituting the tooth root-bone interface and coordinates tooth eruption in a manner dependent on signaling by parathyroid hormone-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR). However, the identity of mesenchymal progenitor cells in the DF and how they are regulated by PTHrP-PPR signaling remain unknown. Here, we show that the PTHrP-PPR autocrine signal maintains physiological cell fates of DF mesenchymal progenitor cells to establish the functional periodontal attachment apparatus and orchestrates tooth eruption. A single-cell RNA-seq analysis revealed cellular heterogeneity of PTHrP+ cells, wherein PTHrP+ DF subpopulations abundantly express PPR. Cell lineage analysis using tamoxifen-inducible PTHrP-creER mice revealed that PTHrP+ DF cells differentiate into cementoblasts on the acellular cementum, periodontal ligament cells, and alveolar cryptal bone osteoblasts during tooth root formation. PPR deficiency induced a cell fate shift of PTHrP+ DF mesenchymal progenitor cells to nonphysiological cementoblast-like cells precociously forming the cellular cementum on the root surface associated with up-regulation of Mef2c and matrix proteins, resulting in loss of the proper periodontal attachment apparatus and primary failure of tooth eruption, closely resembling human genetic conditions caused by PPR mutations. These findings reveal a unique mechanism whereby proper cell fates of mesenchymal progenitor cells are tightly maintained by an autocrine system mediated by PTHrP-PPR signaling to achieve functional formation of skeletal tissues.

Parathyroid hormone-related peptide (1-34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development.

Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone-related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1-34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1-34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1-34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/ß-catenin pathway. PTHrP (1-34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1-34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1-34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/ß-catenin pathway.

Clinical and x-ray oral evaluation in patients with congenital Zika Virus

Abstract Objective: The aim of this study was to investigate possible malformations in the soft, bone and/or dental tissues in patients with congenital Zika Virus (ZIKV) by clinical and x-ray evaluation. Methodology: Thirty children born with ZIKV and 30 children born without ZIKV (control group) were included in the study. Patients were evaluated over 24 consecutive months according to the variables: sex, age, cleft palates, soft tissue lesions, alveolar ridge hyperplasia, short labial and lingual frenums, inadequate posture of the lingual and perioral muscles at rest, micrognathia, narrow palatine vaults, changes in the teeth shape and/or number, sequence eruption, spasms, seizures and eruption delay were evaluated. Chi-square test, Student's t-test and nominal logistic regression were used (p<0.05). Results: Among the 30 babies examined, the mean age of the first dental eruption was 10.8±3.8 with almost two-thirds of the children (n=18, 60%) experiencing eruptions of their first tooth after 9 months of age, nine children (30%) had inadequate lingual posture at rest, more than half of the children (n=18, 60%) had short labial or lingual frenums. ZIKV babies showed a high prevalence of clef palate (p<0.001), inadequate lingual posture at rest (p=0.004), micrognathia (p=0.002), changes in the shape and/or number of teeth (p=0.006), alteration in sequence of dental eruption (p<0.001) and muscles spasms (p=0.002). The delay eruption was associated with inadequate lingual posture at rest (p=0.047), micrognathia (p=0.002) and changes in the shape and/or number of teeth (p=0.021). The delayed eruption (p=0.006) and narrow palatine vaults (p=0.008) were independently associated with ZIKV. Moreover, female patients showed the most narrow palatine vaults (p=0.010). Conclusions: The children with ZIKV showed a greater tendency to have delayed eruption of the first deciduous tooth, inadequate lingual posture and short labial and lingual frenums.

Tooth formation and eruption - lessons learnt from cleidocranial dysplasia.

The principles of formation, renewal, and eruption of teeth are discussed. Numerous genetic aberrations may affect the formation and eruption of teeth. Cleidocranial dysplasia (CCD), caused by mutations in the runt-related transcription factor 2 (RUNX2) gene, is such a condition. The dental phenotype includes problems in both tooth formation (multiple supernumerary permanent teeth) and tooth eruption (lack of shedding of primary teeth and delayed or arrested eruption of permanent teeth). Clinical studies, animal models, and molecular biology studies have documented that RUNX2 is of paramount importance for osteoblast differentiation, for regression of the dental lamina, and for osteoclastogenesis in the dental follicle and the periodontal ligament. Jensen & Kreiborg, 25 yr ago, proposed a treatment strategy to be applied to patients with CCD, focussing on the importance of early treatment to promote spontaneous eruption of permanent teeth through extraction of primary teeth, surgical removal of supernumerary teeth, and removal of bone covering the first formed permanent teeth at the time when root formation of the permanent teeth has reached half or two-thirds of their final length. This strategy still seems valid and seems to lead to reduction in the burden of care for patients compared with the treatment protocols otherwise recommended.

Timing of permanent tooth emergence is associated with overweight/obesity in children from the amazon region

Abstract The aim of this study was to evaluate the association between timing of permanent tooth emergence with overweight and obesity in children from Brazilian Amazon region. The studied population consisted of 192 children, 09 to 12 year-old, from public schools at Manaus, Amazonas-Brazil. Clinical examination was performed and the tooth emergence was evaluated according to the number of permanent erupted teeth. Body mass index z-score was calculated. For the statistical analysis 'Overweight/obese' group was compared with 'Normal weight' group in a case to control ratio 1:2. The t-test based on age was used for means comparison between the groups. A linear regression analysis using age and gender as co-variants was used. The established alpha was 5%. One hundred twenty-seven children were classified as normal weight and 65 were classified as overweight/obese (49 were overweight and 16 were obese). Overweight/obesity condition was associated with the gender, in which boys had a higher chance to present higher weight conditions (OR=1.84; CI 95% 1.06-3.37; p=0.04). The mean number of permanent teeth was higher in the overweight/obesity group (p<0.001). Linear regression analysis demonstrated that nutritional status, gender and age were strongly associated with number of permanent erupted teeth (p<0.05). In conclusion, our study demonstrated that timing of permanent tooth emergence is associated with overweigh/obesity in children from Manaus, Brazil.

Resumo O objetivo deste estudo foi avaliar se a erupção dentária está associada com sobrepeso/obesidade em crianças da região Amazônica brasileira. A população estudada foi composta por 192 crianças, de 9 a 12 anos, de escolas públicas de Manaus, Amazonas-Brasil. O exame clínico foi realizado e a erupção dentária foi avaliada de acordo com o número de dentes permanentes irrompidos. O índice de massa corporal escore-z foi calculado. Para a análise estatística, comparou-se o grupo "sobrepeso / obesidade" com o grupo "peso normal" em uma proporção de controle 1: 2. O teste t baseado na idade foi utilizado para comparação das médias entre os grupos. Uma análise de regressão linear usando idade e sexo como co-variáveis foi utilizada. O alfa estabelecido foi de 5%. Cento e vinte e sete crianças foram classificadas com peso normal e 65 foram classificados com sobrepeso / obesidade (49 com sobrepeso e 16 com obesidade). A condição de sobrepeso / obesidade associou-se ao gênero, no qual os meninos tiveram maior chance de apresentar condições de maior peso (OR = 1,84; IC 95% 1,06-3,37; p = 0,04). O número médio de dentes permanentes irrompidos foi maior no grupo sobrepeso / obesidade (p <0,001). A análise de regressão linear demonstrou que o estado nutricional, sexo e idade foram fortemente associados ao número de dentes permanentes irrompidos (p <0,05). Concluindo, nosso estudo demonstrou que o momento da erupção dos dentes permanentes é associado com sobrepeso / obesidade em crianças de Manaus, Brasil.

Role of the Inferior Alveolar Nerve in Rodent Lower Incisor Stem Cells.

In developing teeth, the sequential and reciprocal interactions between epithelial and mesenchymal tissues promote stem/progenitor cell differentiation. However, the origin of the stem/progenitor cells has been the subject of considerable debate. According to recent studies, mesenchymal stem cells originate from periarterial cells and are regulated by neurons in various organs. The present study examined the role of innervation in tooth development and rodent incisor stem/progenitor cell homeostasis. Rodent incisors continuously grow throughout their lives, and the lower incisors are innervated by the inferior alveolar nerve (IAN). In this study, we resected the IAN in adult rats, and the intact contralateral side served as a nonsurgical control. Sham control rats received the same treatment as the resected rats, except for the resection process. The extent of incisor eruption was measured, and both mesenchymal and epithelial stem/progenitor cells were visualized and compared between the IAN-resected and sham-operated groups. One week after surgery, the IAN-resected incisors exhibited a chalky consistency, and the eruption rate was decreased. Micro-computed tomography and histological analyses performed 4 wk after surgery revealed osteodentin formation, disorganized ameloblast layers, and reduced enamel thickness in the IAN-resected incisors. Immunohistochemical analysis revealed a reduction in the CD90- and LRIG1-positive mesenchymal cell ratio in the IAN-resected incisors. However, the p40-positive epithelial stem/progenitor cell ratio was comparable between the 2 groups. Thus, mesenchymal stem/progenitor cell homeostasis is more related to IAN innervation than to epithelial stem/progenitor cells. Furthermore, sensory nerve innervation influences subsequent incisor growth and formation.