Exposure of pregnant rats to stress and/or sertraline: Side effects on maternal health and neurobehavioral development of male offspring.

AIMS: Sertraline (SE) is one of the most prescribed medications for treating gestational depression, anxiety and stress. However, little is known about its effects on nervous-system development in offspring. Therefore, this study investigated the somatic, reflex and neurobehavioral development of rats exposed to SE during pregnancy, associated or not with stress. MAIN METHODS: Pregnant Wistar rats were assigned to the following groups (n = 10-8 rats/group): CO - control animals administered filtered water by gavage; SE - animals administered 20 mg/kg SE by gavage; ST - animals subjected to restraining stress and administered filtered water; ST/SE - animals subjected to restraining stress and administered 20 mg/kg SE. The treatment was administered between gestational days (GD) 13 to 20. Somatic and reflex developments were investigated in the male offspring from postnatal day (PND) 1 to 21. The elevated plus maze was performed on PND 25 and 80. The open field and light/dark box test were performed on PND 90 and 100, respectively. KEY FINDINGS: Body weight reduction and vaginal bleeding were observed in pregnant rats exposed to SE. The male offspring of the SE group showed delay in incisor eruption, fur development and negative geotaxis. In addition, the SE group was less exploratory (anxious personality) compared to the CO and ST groups. SIGNIFICANCE: The results obtained in the present study demonstrate that sertraline not only impairs maternal health, but also, associated or not with stress, can compromise the somatic, reflex and neurobehavioral development of male rats.

Prospective cohort study of regenerative potential of non vital immature permanent maxillary central incisors using platelet rich fibrin scaffold.

Regenerative endodontic procedures have gained momentum as a treatment modality of young immature permanent teeth. Literature reports reveal that platelet-rich fibrin (PRF) stimulates growth factors and induces regeneration. This study was undertaken to assess the regenerative potential of non-vital immature permanent maxillary central incisors using PRF with a follow-up for 2 yrs. 19 patients in the age group of 9-25 yrs with immature, non-vital permanent maxillary central incisors (n = 23) with/without signs and/or symptoms of periapical pathosis and open apex were included in this study. In the first appointment, access opening, canal disinfection and triple antibiotic paste placement were done. In the subsequent visit, PRF was prepared and placed inside the canal. Access was sealed with Mineral trioxide aggregate plug and composite. The patient was reviewed up to 24 mths. The mean difference was statistically analyzed using Friedman test followed by Dunn post hoc test and adjusted by Bonferroni correction (p < 0.05). As per AAE guidelines, the primary and secondary goals were achieved. A significant (p < 0.001) gradual increase in the root length, thickness of dentinal walls and decrease in apical diameter were observed. Within the limitations of this study, PRF placement was clinically and radiographically effective in inducing regeneration of non-vital immature permanent teeth.

Sox2 controls asymmetric patterning of ameloblast lineage commitment by regulation of FGF signaling in the mouse incisor.

Mouse incisors are covered by enamel only on the labial side and the lingual side is covered by dentin without enamel. This asymmetric distribution of enamel makes it possible to be abrased on the lingual side, generating the sharp cutting edge of incisor on the labial side. The abrasion of mouse incisors is compensated by the continuous growth throughout life. Epithelium stem cells responsible for its continuous growth are reported to localize within the labial cervical loop. The transcription factor Sox2 plays important roles in the maintenance of stem cell pluripotency and organ formation. We previously found that Sox2 mainly expressed in the dental epithelium. Besides, Sox2 has been reported to be a dental epithelium stem cell marker in the incisor. However, the exact mechanism of Sox2 controlling amelogenesis is still not quite clearly elucidated. Here we report that conditional deletion of Sox2 in the dental epithelium using Shhcre caused impaired ameloblast differentiation in the labial side and induced ectopic ameloblast-like cell differentiation on the lingual side. Abnormal FGF gene expression was detected by RNAscope in situ hybridization in the mutant incisor. Collectively, we speculate that asymmetric ameloblast lineage commitment of mouse incisor might be regulated by Sox2 through FGF signaling.

Gene-environment interaction in molar-incisor hypomineralization.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.

An inconstant biorhythm: The changing pace of Retzius periodicity in human permanent teeth.

OBJECTIVES: Human tooth enamel retains evidence of growth in the form of Retzius lines. The number of daily growth increments between the regularly occurring lines defines their repeat interval, or periodicity. Retzius periodicity is often incorporated into enamel formation times, age-at-death reconstructions, or used to provide a basis from which to explore an underlying biorhythm. Biological anthropologists typically assume that RP remains constant within an individual and does not vary along the tooth-row. Here, we test that assumption. MATERIALS AND METHODS: RP was calculated from n = 223 thin sections of human permanent teeth from individuals of British and southern African origin. Forty individuals provided multiple teeth (n = 102 teeth) and a further 121 individuals each provided a single tooth. RESULTS: We report first evidence that RP of permanent teeth does not always remain constant within an individual. Of those individuals that provided multiple teeth, 42% (n = 17/40) demonstrated a decrease in RP along the tooth row, with most shifting by two or more days (n = 11). Across the entire sample, mean RP of anterior teeth was significantly higher than molars. Mean premolar RP tended to be intermediate between anterior teeth and molars. DISCUSSION: Our data do not support the assumption that RP invariably remains constant within the permanent teeth of an individual. Transferring RP from molars to incisors within an individual can result in a miscalculation of formation time and age-at-death by up to 1 year. Implications for biological anthropologists and the source of the underlying long period biorhythm are discussed.

Odontoblast processes of the mouse incisor are plates oriented in the direction of growth.

Odontoblast processes are thin cytoplasmic projections that extend from the cell body at the periphery of the pulp toward the dentin-enamel junction. The odontoblast processes function in the secretion, assembly and mineralization of dentin during development, participate in mechanosensation, and aid in dentin repair in mature teeth. Because they are small and densely arranged, their three-dimensional organization is not well documented. To gain further insight into how odontoblast processes contribute to odontogenesis, we used serial section electron microscopy and three-dimensional reconstructions to examine these processes in the predentin region of mouse molars and incisors. In molars, the odontoblast processes are tubular with a diameter of ~1.8 µm. The odontoblast processes near the incisor tip are similarly shaped, but those midway between the tip and apex are shaped like plates. The plates are radially aligned and longitudinally oriented with respect to the growth axis of the incisor. The thickness of the plates is approximately the same as the diameter of molar odontoblast processes. The plates have an irregular edge; the average ratio of width (midway in the predentin) to thickness is 2.3 on the labial side and 3.6 on the lingual side. The plate geometry seems likely to be related to the continuous growth of the incisor and may provide a clue as to the mechanisms by which the odontoblast processes are involved in tooth development.

Maxillary incisor enamel defects in individuals born with cleft lip/palate.

Cleft lip with or without cleft palate (CLP) is considered the most frequent congenital malformations of the head and neck, with cleft individuals exhibiting more chances of presenting abnormalities such as developmental defects of enamel (DDE). Matrix metallopeptidase 2 (MMP2) is a membrane-bound protein with collagen-degrading ability and has important roles in tooth formation and mineralization. The aim of this study was to evaluate the frequency, location, severity and extent of DDE found in the maxillary incisors for groups of individuals born with CLP, as well as understanding their relationship with the cleft side. Besides, this study addresses the hypothesis that DDE can be influenced by variation in the MMP2 genes (rs9923304). Individual samples, clinical history, intraoral photographs and panoramic radiographs were obtained from 233 patients under treatment at the Cleft Lip and Palate Service of the University Hospital Lauro Wanderley at the Federal University of Paraíba. Digital images were examined by the same evaluator using the Classification of Defects According to the Modified DDE Index, and then loaded into the Image Tool software, where two measurements were made: total area of the buccal surface (SA) and the area of the DDE (DA), obtaining the percentage of the surface area affected (%SAD) (ICC = 0.99). Genomic DNA was extracted from saliva samples from 124 participants. Genotyping was carried out using TaqMan chemistry for one marker in MMP2 (rs9923304). Statistical analyses were performed by The Jamovi Project software. The Shapiro-Wilk test was applied, followed by the Student's t-test and the Mann-Whitney test. Chi-square and Fisher's exact tests, and odds ratio (OR) with 95% confidence interval (CI) calculations were used to determine Hardy-Weinberg equilibrium and statistically significant differences with an alpha of 0.05. No significant differences in the prevalence and extent of enamel defects were found between male and female individuals born with CLP (p = 0.058256). The frequency of individuals presenting teeth with DDE, in relation to the cleft and non-cleft side, was statistically different (p <0.001; OR = 7.15, CI: 4.674> 7.151> 10.942). However, the averages of %SAD were similar (p = 0.18). The highest means of the %SAD were found in individuals with bilateral cleft lip with or without cleft palate (BCLP) when compared to individuals with unilateral cleft lip with or without cleft palate (UCLP), for the teeth inside (IA) and outside the cleft area (OA) (p <0.001). Regardless of the cleft side, individuals with BCLP were 7.85 times more likely to have more than one third of the tooth surface affected, showing more frequently defects in the three thirds (OA: p <0.001) (IA: p = 0.03), as well as a higher frequency of more than one type of defect (OA: p = 0.000358) (IA: p = 0.008016), whereas in UCLP, defects were isolated and restricted to only one third, more frequently, the incisal third (OA: p = 0.009) (IA: p = 0.001), with greater frequency of milder defects, such as demarcated (p = 0.02) and diffuse (p = 0.008) opacities. A higher frequency of the T allele, less common, was observed in the group of CLP individuals who had all the affected teeth or at least two teeth with %SAD greater than 20% (p = 0.019843). Our results suggest that MMP2 may have a role in the cases that presented DDE and genotyping rs9923304 could serve as the basis for a genomic approach to define risks for individuals born with CLP. Frequency and severity of DDE is strongly related to the CLP phenotype, since the highest values were found for BCLP. However, the extent of the DDE is independent of its relationship with the side of the cleft.

Epithelial loss of mitochondrial oxidative phosphorylation leads to disturbed enamel and impaired dentin matrix formation in postnatal developed mouse incisor.

The formation of dentin and enamel matrix depends on reciprocal interactions between epithelial-mesenchymal cells. To assess the role of mitochondrial function in amelogenesis and dentinogenesis, we studied postnatal incisor development in K320E-TwinkleEpi mice. In these mice, a loss of mitochondrial DNA (mtDNA), followed by a severe defect in the oxidative phosphorylation system is induced specifically in Keratin 14 (K14+) expressing epithelial cells. Histochemical staining showed severe reduction of cytochrome c oxidase activity only in K14+ epithelial cells. In mutant incisors, H&E staining showed severe defects in the ameloblasts, in the epithelial cells of the stratum intermedium and the papillary cell layer, but also a disturbed odontoblast layer. The lack of amelogenin in the enamel matrix of K320E-TwinkleEpi mice indicated that defective ameloblasts are not able to form extracellular enamel matrix proteins. In comparison to control incisors, von Kossa staining showed enamel biomineralization defects and dentin matrix impairment. In mutant incisor, TUNEL staining and ultrastructural analyses revealed differentiation defects, while in hair follicle cells apoptosis is prevalent. We concluded that mitochondrial oxidative phosphorylation in epithelial cells of the developed incisor is required for Ca2+ homeostasis to regulate the formation of enamel matrix and induce the differentiation of ectomesenchymal cells into odontoblasts.

Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth.

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.

MicroRNA-31 regulates dental epithelial cell proliferation by targeting Satb2.

MicroRNAs (miRNAs) exhibit strong potential clinical application owing to their extensive regulation and flexible delivery properties. MicroRNA-31 (miR-31) is an evolutionarily conserved miRNA expressed during tooth development, and it is highly expressed in mouse incisor epithelium. The specific role of miR-31 in odontogenesis has not been elucidated comprehensively, and the aim of the present study was to investigate its activity. Our results showed that miR-31 suppressed LS8 cell proliferation by inhibiting the cell cycle at the G1/S transition. Mutation of Special AT-rich sequence-binding protein 2 (SATB2) gene is responsible for human SATB2-associated syndrome (SAS), which is often accompanied by dental abnormities. Here, it was identified as a direct target of miR-31 in LS8 cells and a promoter of cell proliferation. The expression and distribution of SATB2 in mouse molars and incisors were explored using immunofluorescence, which showed strong signals in the nuclei of incisor epithelial cells and weak signals in the cytoplasm of molar epithelial cells. Moreover, rescue experiments demonstrated that Satb2 could mitigate the inhibitory effect of miR-31 on cell proliferation by promoting the expression of CDK4. Collectively, our results suggested that miR-31 regulates dental epithelial cell proliferation by targeting Satb2, highlighting the biological importance of miR-31 in odontogenesis.

A study on the morphologic change of palatal alveolar bone shape after intrusion and retraction of maxillary incisors.

The purpose of this study is to evaluate the changes in the palatal alveolar bone thickness and find the factors related to the resorption of the palatal alveolar bone caused by tooth movement after the maxillary incisors were retracted and intruded during orthodontic treatment. The study group comprised of 33 skeletal Class II malocclusion patients who underwent extraction for orthodontic treatment. Palatal alveolar bone thickness changes and resorption factors were identified and analyzed. The changes of maxillary central incisors and palatal alveolar bone thickness were measured, and the corresponding sample t test was performed using SPSS (IBM SPSS version 22). The amount of palatal alveolar bone resorption was measured and various parameters were analyzed to determine which factors affected it. Correlation analysis adopting the amount of palatal alveolar bone resorption as a dependent variable demonstrated that the SNB, mandibular plane angle, and the inclination of the maxillary central incisor were significantly correlated with before treatment. On the other hand, mandibular plane angle, angle of convexity, the inclination of the upper incisor, and the occlusal plane (UOP, POP) were significantly correlated with post-treatment. In addition, the variables related to palatal contour (PP to PAS, SN to PAS, palatal surface angle) and occlusal planes (UOP/POP) were significantly correlated with the difference in palatal bone resorption. During initial diagnosis, high angle class II with normal upper incisor inclination can be signs of high-risk factors. In addition, maintaining the occlusal plane during treatment helps to prevent palatal bone loss.

Effects of lipid metabolism on mouse incisor dentinogenesis.

Tooth formation can be affected by various factors, such as oral disease, drug administration, and systemic illness, as well as internal conditions including dentin formation. Dyslipidemia is an important lifestyle disease, though the relationship of aberrant lipid metabolism with tooth formation has not been clarified. This study was performed to examine the effects of dyslipidemia on tooth formation and tooth development. Dyslipidemia was induced in mice by giving a high-fat diet (HFD) for 12 weeks. Additionally, LDL receptor-deficient (Ldlr-/-) strain mice were used to analyze the effects of dyslipidemia and lipid metabolism in greater detail. In the HFD-fed mice, incisor elongation was decreased and pulp was significantly narrowed, while histological findings revealed disappearance of predentin. In Ldlr-/- mice fed regular chow, incisor elongation showed a decreasing trend and pulp a narrowing trend, while predentin changes were unclear. Serum lipid levels were increased in the HFD-fed wild-type (WT) mice, while Ldlr-/- mice given the HFD showed the greatest increase. These results show important effects of lipid metabolism, especially via the LDL receptor, on tooth homeostasis maintenance. In addition, they suggest a different mechanism for WT and Ldlr-/- mice, though the LDL receptor pathway may not be the only factor involved.

Adaptive amelogenesis during unimpeded eruption of rat mandibular incisor.

The aim of the study was to see whether the length of the enamel secretion zone in unimpeded rat incisors, measured precisely, is in agreement with the observed decrease in enamel thickness. Unimpeded eruption of mandibular incisors of five experimental and two control rats was induced by cutting off the erupted part of the incisors three times per week for 5 weeks. The length of the zone of enamel secretion in unimpeded and impeded control incisors was measured on longitudinal and serial transverse histological sections of fixed, demineralised and embedded hemimandibles. Impeded contralateral incisors were also included in the study. The length of the zone of enamel secretion in unimpeded incisors showed an increase to 8,398 ± 558 µm, that is 161% of the length in control incisors (5,213 ± 95 µm). The contralateral incisor showed a reduction in eruption rate, in length of the secretion zone, and the whole tooth was shifted somewhat apically. The measured length of the secretion zone is in agreement with the observed thickness of enamel (98 µm) in unimpeded incisors. The reduced eruption rate and the apical shift of the contralateral incisor are probably due to an increased occlusal load.

Survival and complication analyses of avulsed and replanted permanent teeth.

This retrospective clinical study investigated the survival probability of avulsed and replanted permanent teeth in relation to functional healing, replacement and inflammatory resorption. The explorative data analysis included data from 36 patients and 49 replanted permanent teeth with a minimum observation time of 60 days; the patients were generally treated according to the current guidelines of the International Association of Dental Traumatology at the university hospital in Munich, Germany, between 2004 and 2017. The mean observation period was 3.5 years. Functional healing was observed in 26.5% (N = 13/49) of the included avulsion cases. In comparison, replacement resorption affected 51.0% (N = 25/49) of the replanted teeth, of which 24.0% (N = 6/25) were lost over the course of years (mean, 6.1 years). In contrast, inflammatory resorption resulted in the early loss of all replanted teeth (mean, 1.7 years) and affected 22.5% (N = 11/49) of all the monitored teeth. Therefore, it can be concluded that tooth avulsion remains a severe dental injury with an unpredictable prognosis. This topic demands further fundamental research aiming to maintain and/or regenerate the periodontal ligament after tooth avulsion, particularly in association with non-physiological tooth rescue.

Pivotal Role of Tenascin-W (-N) in Postnatal Incisor Growth and Periodontal Ligament Remodeling.

The continuously growing mouse incisor provides a fascinating model for studying stem cell regulation and organ renewal. In the incisor, epithelial and mesenchymal stem cells assure lifelong tooth growth. The epithelial stem cells reside in a niche known as the cervical loop. Mesenchymal stem cells are located in the nearby apical neurovascular bundle and in the neural plexus. So far, little is known about extracellular cues that are controlling incisor stem cell renewal and guidance. The extracellular matrix protein tenascin-W, also known as tenascin-N (TNN), is expressed in the mesenchyme of the pulp and of the periodontal ligament of the incisor, and is closely associated with collagen 3 fibers. Here, we report for the first time the phenotype of tenascin-W/TNN deficient mice, which in a C57BL/6N background exhibit a reduced body weight and lifespan. We found major defects in the alveolar bone and periodontal ligament of the growing rodent incisors, whereas molars were not affected. The alveolar bone around the incisor was replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, less food intake and reduced body weight. Using soft food to reduce mechanical load on the incisor partially rescued the phenotype. In situ hybridization and Gli1 reporter mouse experiments revealed decreased hedgehog signaling in the incisor mesenchymal stem cell compartment, which coordinates the development of mesenchymal stem cell niche. These results indicate that TNN deficiency in mice affects periodontal remodeling and increases nerve fiber branching. Through periodontal pain the food intake is reduced and the incisor renewal and the neurovascular sonic hedgehog secretion rate are reduced. In conclusion, tenascin-W/TNN seems to have a primary function in rapid periodontal tissue remodeling and a secondary function in mechanosensation.

Remote Corticotomy Accelerates Orthodontic Tooth Movement in a Rat Model.

INTRODUCTION: With an increasing demand for orthodontic treatment for adult patients, orthodontic professionals are constantly seeking novel strategies and technologies that can accelerate tooth movement in order to shorten the treatment period. For instance, in recent years, the influences of different surgical techniques on orthodontic tooth movement in the ipsilateral side of surgery were intensively investigated. Here, we attempt to examine if corticotomy could also affect the rate of tooth movement in the contralateral side of the surgery by using a rodent model. MATERIALS AND METHODS: 72 eight-week-old Sprague-Dawley rats were randomly divided into three groups as follows: the Control group (orthodontic treatment devices delivered only, no tooth movement), the orthodontic tooth movement (OTM) group (orthodontic treatment devices delivered and orthodontic treatment performed), and the Corticotomy + OTM group (remote corticotomy performed, orthodontic treatment devices delivered, followed by orthodontic treatment). The surgical procedure was conducted on the right side of the maxilla at the time of appliance placement and a force of 60 g was applied between the maxillary left first molar and maxillary incisors using nickel-titanium springs to stimulate OTM. The OTM distance and speed were tracked at 3, 7, 14, and 28 days post-surgery, followed by histological and immunohistochemical assessments. RESULTS: In comparison with orthodontic treatment only, the contralateral corticotomy significantly accelerated OTM. Furthermore, animals undergoing corticotomy + OTM presented with a greater number of osteoclasts on the compression side, stronger staining of the osteogenic marker on the tension side, and higher expression of an inflammatory marker than the OTM group animals. CONCLUSION: Our current study demonstrates that remote corticotomy effectively accelerates alveolar bone remodeling and OTM. The study enriches our understanding of the regional acceleratory phenomenon (RAP) and offers an alternative strategy for accelerating OTM to shorten the orthodontic treatment period.

BMP Signaling in Regulating Mesenchymal Stem Cells in Incisor Homeostasis.

Bone morphogenetic protein (BMP) signaling performs multiple essential functions during craniofacial development. In this study, we used the adult mouse incisor as a model to uncover how BMP signaling maintains tissue homeostasis and regulates mesenchymal stem cell (MSC) fate by mediating WNT and FGF signaling. We observed a severe defect in the proximal region of the adult mouse incisor after loss of BMP signaling in the Gli1+ cell lineage, indicating that BMP signaling is required for cell proliferation and odontoblast differentiation. Our study demonstrates that BMP signaling serves as a key regulator that antagonizes WNT and FGF signaling to regulate MSC lineage commitment. In addition, BMP signaling in the Gli1+ cell lineage is also required for the maintenance of quiescent MSCs, suggesting that BMP signaling not only is important for odontoblast differentiation but also plays a crucial role in providing feedback to the MSC population. This study highlights multiple important roles of BMP signaling in regulating tissue homeostasis.

Longitudinal Quantitation of Tooth Displacement in Chinese Adolescents with Normal Occlusion.

This longitudinal study aims to analyze the different modes of the maxillary and mandibular tooth displacement in subjects, who were aged 12.5-17.5 years (150-210 months), with untreated normal (Class I) occlusion. Longitudinal lateral cephalograms for a set of 10 subjects (7 females and 3 males) at consecutive annual time points were selected and monitored. Data were analyzed on the basis of the superimpositions of serial tracings of lateral cephalograms on stable anterior cranial base, the anatomies of the maxillary and mandibular structures. The horizontal and vertical displacements of the first molar and incisor were assessed by t-test. The local and the secondary tooth displacements with growth contributed to the total horizontal and vertical displacements of the molars and incisors of the subjects. In the total tooth displacement, the horizontal growth of maxilla and mandible had the same contribution as the local tooth displacements. The vertical maxillary growth played a smaller role than the local drift, and mandibular remodeling went in a reverse direction with the local tooth drift. The first molars moved more forward than the incisors in the upper and lower arches. Both the upper and lower first molars showed forward tipping. The analysis of tooth displacement may be utilized in making orthodontic treatment plan, including anchorage or torque control.

Developmental Disturbance of a Maxillary Permanent Lateral Incisor Following Trauma at the Age of 16 Months: A 6-Year Follow-Up.

A 3 year and 8 months old Chinese boy was referred for a consultation regarding his missing maxillary anterior teeth. He had a history of trauma to his primary maxillary anterior teeth due to a fall at the age of 16 months. Clinical examination of the patient indicated multiple carious lesions and inadequate oral hygiene. Radiographic examination revealed intrusion of the primary left lateral incisor, with evidence of damage to the permanent tooth germ. Subsequently, the patient was followed-up for almost six years during which his permanent maxillary left lateral incisor erupted exhibiting an unusual morphology. Clinically enamel hypoplasia and radiographically dens invaginatus were evident in affected tooth.

IFT80 is required for stem cell proliferation, differentiation, and odontoblast polarization during tooth development.

Primary cilia and intraflagellar transport (IFT) proteins control a wide variety of processes during tissue development and homeostasis. However, their role in regulation of stem cell properties during tooth development remains elusive. Here, we revealed that dental pulp stem cells (DPSCs) express IFT80, which is required for maintaining DPSC properties. Mice with deletion of IFT80 in odontoblast lineage show impaired molar root development and delayed incisor eruption through reduced DPSC proliferation and differentiation, and disrupted odontoblast polarization. Impaired odontoblast differentiation resulted from disrupted hedgehog (Hh) signaling pathways. Decreased DPSC proliferation is associated with impaired fibroblast growth factor 2 (FGF2) signaling caused by loss of IFT80, leading to the disruption of FGF2-FGFR1-PI3K-AKT signaling in IFT80-deficient DPSCs. The results provide the first evidence that IFT80 controls tooth development through influencing cell proliferation, differentiation, and polarization, and Hh and FGF/AKT signaling pathways, demonstrating that IFT proteins are likely to be the new therapeutic targets for tooth and other tissue repair and regeneration.