Jurassic fossil juvenile reveals prolonged life history in early mammals.

Living mammal groups exhibit rapid juvenile growth with a cessation of growth in adulthood1. Understanding the emergence of this pattern in the earliest mammaliaforms (mammals and their closest extinct relatives) is hindered by a paucity of fossils representing juvenile individuals. We report exceptionally complete juvenile and adult specimens of the Middle Jurassic docodontan Krusatodon, providing anatomical data and insights into the life history of early diverging mammaliaforms. We used synchrotron X-ray micro-computed tomography imaging of cementum growth increments in the teeth2-4 to provide evidence of pace of life in a Mesozoic mammaliaform. The adult was about 7 years and the juvenile 7 to 24 months of age at death and in the process of replacing its deciduous dentition with its final, adult generation. When analysed against a dataset of life history parameters for extant mammals5, the relative sequence of adult tooth eruption was already established in Krusatodon and in the range observed in extant mammals but this development was prolonged, taking place during a longer period as part of a significantly longer maximum lifespan than extant mammals of comparable adult body mass (156 g or less). Our findings suggest that early diverging mammaliaforms did not experience the same life histories as extant small-bodied mammals and the fundamental shift to faster growth over a shorter lifespan may not have taken place in mammaliaforms until during or after the Middle Jurassic.

Etiological Mechanisms and Genetic/Biological Modulation Related to PTH1R in Primary Failure of Tooth Eruption.

Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.

Global variations in eruption chronology of permanent teeth: A systematic review and meta-analysis.

OBJECTIVES: Population-based variations have been reported in permanent teeth eruption but only sparse literature exists on the same. A systematic review and meta-analysis were performed to assess the global variations in eruption chronology of permanent teeth in children and adolescents and the role of sexes, jaws and classes of socio-economic status (SES) on timing of eruption was explored. METHODS: The protocol for the systematic review was registered in PROSPERO. An extensive search of PubMed, EMBASE, Google Scholar, EBSCO, Cochrane library, and anthropology databases was carried out until April 2023. Additionally, grey literature search and hand-searching of relevant key journals was done. RESULTS: Overall, 3797 cross-sectional and longitudinal studies were retrieved from multiple databases. A total of 939, 191 participants were included from 80 studies of which, 41 were carried out in Asia, 26 in Europe, 5 in Africa, 4 in North America, and 4 in Oceania. The mandibular first molar eruption was found to be as early as 4.09 years while the maxillary second molar erupted as late as 13.45 years. Using a random effects model, 28 forest plots were generated. Meta-regression interpreted tooth eruption to be earlier in females and in the mandible. CONCLUSIONS: The findings of this study show that the ages of permanent teeth eruption was advanced in the European population followed by Africa and Asia.

Assessing current clinical eruption stage of mandibular third molars by dental panoramic radiography.

OBJECTIVE: We examined whether dental panoramic radiography (PAN) can be used to identify the clinical stage of eruption of mandibular third molars at the time of radiological examination. MATERIALS AND METHODS: Cross-sectional data included records from clinical oral examination and PANs of university students. In the retrospective analysis of 345 mandibular third molars in 189 participants (20% men, 80% women; mean age 20.7 years; standard deviation [SD] ± 0.6), clinical stages of eruption were compared with their radiographic depth in bone, inclination, and root development. Statistics included χ2, Mann-Whitney U tests, and logistic regression. RESULTS: Significant (p < 0.001) predictor variables for assessing the clinical stage of eruption were radiographic depth in bone and inclination. All teeth radiologically at a depth of the cementoenamel (CE) junction of the neighbouring second molar or deeper were clinically unerupted. Above the CE junction, 80% of vertical and 97% of distoangular teeth were connected to the oral cavity, and 82% of mesioangular and 69% of horizontal teeth were clinically unerupted. CONCLUSION: All teeth below or at the CE junction are clinically unerupted. Above the CE junction, stage of eruption should be assessed together with the inclination, but horizontally inclined teeth are recommended to be verified clinically.

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.

Comparison of the mandibular retromolar space in adults with different sagittal skeletal types and eruption patterns of the mandibular third-molar: a cone-beam computed tomography study.

BACKGROUND: The mandibular retromolar space (RMS) has not been extensively studied in relation to various sagittal skeletal classes and patterns of third-molar eruption. The objective of this study was to test the null hypothesis that there is no difference in the mandibular RMS among normodivergent subjects with different skeletal classes and patterns of mandibular third-molar eruption, using cone-beam computed tomography (CBCT). METHOD: A total of 105 normodivergent patients (20-40 years) were included in this study. Participants were categorized into Class I, II and III groups based on ANB and further impacted and erupted groups based on the eruption patterns of the mandibular third molars. Measurements of the mandibular RMS were taken at four planes parallel to the occlusal plane, along the cusp line. Comparative analyses were conducted among the three sagittal groups and between the impacted and erupted groups. RESULTS: The Class II group exhibited a statistically smaller RMS (P < 0.05). RMS was found to be larger in third-molar erupted group (P < 0.05). The rates of root contact and third-molar impaction was significantly higher in Class II group. (P < 0.05) CONCLUSIONS: The null hypothesis was rejected. Patients with Skeletal Class II tend to have a smaller mandibular RMS and a higher prevalence of root contact and third-molar impaction. The presence of impacted mandibular third molars was correlated with a shorter RMS. TRIAL REGISTRATION: Retrospectively registered.

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.

Revisiting the human dental follicle: From tooth development to its association with unerupted or impacted teeth and pathological changes.

Dental follicles are involved in odontogenesis, periodontogenesis, and tooth eruption. Dental follicles are unique structures, considering that their remnants can persist within the jawbones after odontogenesis throughout life if the tooth does not erupt. Pathological changes may occur in these tissues as individuals age. The changes range from benign to life threatening. Thus, the assessment of age-related changes in dental follicles associated with unerupted teeth is of paramount importance. In this review, we summarize the physiological roles and changes in dental follicles in odontogenesis, tooth eruption, and aging, in addition to the pathological changes associated with these structures. We encourage investigators to consider this peculiar tissue as a unique model and explore its potential to clarify its importance from the viewpoints of developmental biology, tissue physiology, and pathology.

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.

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.

Early Weight Gain Forecasts Accelerated Eruption of Deciduous Teeth and Later Overweight Status during the First Year.

OBJECTIVES: To determine whether early diet and weight gain velocity have independent or interactive effects on deciduous teeth emergence and overweight status during the first year. STUDY DESIGN: Monthly measures of anthropometry and teeth eruption were collected during a 1-year trial (0.5-12.5 months) on formula-fed infants in which the type of randomized infant formula (cow milk or extensively hydrolyzed protein) diet significantly affected early (0.5-4.5 months) weight gain velocity. Generalized linear mixed models determined whether early diet and weight gain velocity had independent or interactive effects on timing and pattern of teeth eruption. Data from a trial on breastfed infants were used to explore effects of breast milk vs infant formula diets on teeth eruption and overweight status at 10.5 months. RESULTS: Independent of infant formula diet, velocities of weight gain had direct effects on the age of first deciduous tooth (P < .04) and number of erupted teeth over time (P < .002). Greater velocity of weight gain from 0.5 to 4.5 months caused earlier and more frequent eruption of deciduous teeth from 4.5 to 12.5 months. Exploratory follow-up analyses on the breastfed and formula-fed diet groups found early weight gain velocity (P = .001), but not diet or its interaction, had significant effects. Infants in the upper quartile for weight gain velocity had more primary teeth (P = .002), and a greater proportion of them were overweight (P < .001) at 10.5 months. CONCLUSIONS: Faster weight gain accretion forecasted accelerated primary teeth eruption and increased percentage of children who were overweight-risk factors for dental caries and obesity. TRIAL REGISTRATION: ClinicalTrials.govNCT01700205 [2012-2015] and NCT01667549 [2012-2015].

Age at first molar emergence in Pan troglodytes verus and variation in the timing of molar emergence among free-living chimpanzees.

Age at lower first molar (M1) emergence is a commonly used proxy for inferring life-history scheduling in fossil primates, but its utility is dependent on knowing to what extent extant populations vary in this datum and how this variation correlates with the scheduling of life-history variables. Here, we address the first of these issues among extant chimpanzees. While age at M1 emergence has been documented in several live individuals from the Kanyawara population of Pan troglodytes schweinfurthii in Uganda, it has been estimated for only one individual of Pan troglodytes verus, based on a deceased animal from the Taï Forest in Côte d'Ivoire. To further explore interpopulation variation in this variable in chimpanzees, and using dental histology, we calculated ages at death for two wild-shot individuals of P. t. verus with erupting M1, both collected in Liberia during the mid-1950s, and estimated ages at M1 emergence from the ages at death. The overall range for these two individuals is ∼4.2-4.6 yr, compared with an age of ∼3.7 yr for the individual from the Taï Forest, and <2.5-3.3 yr for the several individuals of P. t. schweinfurthii. While the absolute range of ∼2 yr in these samples combined is little greater than in captive chimpanzees, the disparity between the samples of P. t. schweinfurthii and P. t. verus is striking, although it cannot be determined if this disparity represents a subspecies difference or simply population differences expressed in two different subspecies. While life-history data are unavailable for the population to which the Liberian chimpanzees belonged, the difference in M1 emergence ages between these individuals and those from Kanyawara still suggests caution when attempting even broad life-history inference in fossil apes and hominins based on age at M1 emergence.

Age and Sequence of Permanent Teeth Eruption in Lebanese Children.

BACKGROUND: The timing of eruption of permanent teeth can be a precious help to the pediatric practitioner in identifying an appropriate treatment plan. Usually, it presents a more precise sign of an early or late growth of the child. AIMS: It is to determine whether the timing of the permanent teeth eruption in Lebanese pediatric population can be considered as standard Lebanese values, since no other study was previously performed. MATERIALS AND METHODS: A cross-sectional study is conducted, and the clinical emergence data are collected for a sample of 2317 Lebanese children aged between 5.5 years and 13 years (1129 girls and 1188 boys) from different socioeconomic groups in rural and urban communities spread over different regions in Lebanon. The study investigates dental emergence patterns. RESULTS: Statistical analysis is performed with the SPSS Software. A confidence interval of 95% and significance level of 5% are adopted. The trend is for males to begin their permanent teeth eruption later than girls. Emergence of all permanent mandibular teeth is earlier than maxillary ones. Symmetry is found between the right and left teeth in the maxilla, as well as in the mandibula. CONCLUSION: In this study, the results indicate that premolars and second permanent molars erupt earlier in the Lebanese children compared to children of other countries reflected in several studies.

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.

Teething symptoms in children with congenital Zika syndrome: A 2-year follow-up.

BACKGROUND: The eruption of primary teeth represents a stage of many challenges for parents. AIM: To investigate the occurrence of signs and symptoms related to the eruption of the primary dentition in children with congenital Zika syndrome. DESIGN: Longitudinal study developed with 79 children followed up for a period of 24 months. Data on sex, gestational age, low birthweight, microcephaly, signs and symptoms related to the dental eruption phase, and use and type of medication were collected. Data were presented by descriptive and inferential statistics (chi-square test). RESULTS: The majority (94.9%) exhibited simultaneously two or more signs and symptoms related to dental eruption. Increased salivation (91.1%), irritability (86.1%), and gingival itching (83.5%) were the most commonly reported signs and symptoms. Bivariate analysis showed association between elevation of body temperature and sex (P < 0.05). Almost two-thirds of mothers (63.3%) reported using medication to relieve symptoms presented by the child; however, the use of topical medication prevailed (57.1%). CONCLUSION: All children with congenital Zika syndrome presented manifestations related to the eruption of primary teeth, with increased salivation, irritability, and gingival pruritus. The use of ointments and gels was the option of mothers in the treatment of the oral discomfort presented by infants.

Effects of first permanent molar extraction on space changes observed in the dental arch using data mining method.

AIM: The high incidence of caries in first permanent molars (FPMs) makes premature extraction of these teeth common. The extraction of the permanent teeth results in various changes in the dental arch. The aim of this study was to evaluate space closure, the eruption of second permanent molars (SPMs), and changes in dental arch after extraction of the FPMs. MATERIALS AND METHODS: Eruption of 83 SPMs was recorded and radiographically developmental stage of these SPMs in the pre-extraction panoramic radiograph was assessed. Space was measured between the distal surface of the second premolar and the mesial surface of SPM. RESULTS: Out of 55 patients, 28 (50.9%) were males and 27 (49.1%) were females. Thirty-seven (44.6%) of 83 teeth belonged to category 1, 17 (20.5%) teeth belonged to category 2, and 5 (6.02%) teeth belonged to category 3. Although category 4 was not found, 24 (28.9%) teeth were observed to be in category 5. Out of all SPMs, 10.8% represented the ''ideal'' stage of Demirjian's dental development, stage E. CONCLUSION: In patients who had the FPMs extracted before the eruption of the SPM, it is important with regards to the patients' comfort and health to review the patient regularly and to determine any need for orthodontic treatment.

Esthetic treatment of altered passive eruption.

Altered passive eruption is described as a condition in which the relationship between teeth, alveolar bone and soft tissues creates an excessive display of gingiva, commonly known as a 'gummy smile'. While there are authors who consider altered passive eruption to be a risk to periodontal health, its impact is greatest in terms of oral esthetics. The aim of periodontal management in such cases is not only to improve patient esthetics but also to restore periodontal health by re-establishing the normal relationship between the gingival margin, alveolar bone crest and cemento-enamel junction. The aim of this article is to present a narrative review of the etiology, classification and management of altered passive eruption.

Development of the gingival sulcus at the time of tooth eruption and the influence of genetic factors.

Tooth eruption is characterized by a concert of mechanisms that result in the emergence of teeth in the oral cavity. Genetic variants seem to regulate this process and the formation of a gingival sulcus around the teeth. Interindividual variability in the response to microbial triggers in the sulcus plays an important role in the onset and progression of periodontal diseases. Host genetic variants can influence this variability, affecting the response of the host to the subgingival biofilm. Genetic factors affecting tooth eruption could potentially influence susceptibility to periodontal diseases and, specifically, susceptibility to localized aggressive periodontitis. This review aims to discuss the evidence available for the role of host genetic variants in tooth eruption and to and to give some directions for prospective research in this topic.

The WITS Atlas: A Black Southern African dental atlas for permanent tooth formation and emergence.

Current dental maturity charts, such as the widely applied London atlas, do not take into consideration advanced tooth emergence and formation patterns observed in children of African ancestry. The result is inaccurate age estimation in Southern Africa, a region where there is great forensic and anthropological need for reliable age estimation. OBJECTIVES: To develop a population-specific atlas of permanent tooth emergence and formation for age estimation of Black Southern Africans. MATERIALS AND METHODS: Using data from a cross-sectional study of 642 school children aged 5-20 years, panoramic radiographs taken during routine dental examination in a mobile treatment van were analyzed using the Demirjian method of eight (A-H) tooth formation stages. Tables of the stages of tooth development for each tooth, including the third molars, were generated separately for age cohorts and by sex. The most frequently occurring (modal) stage of tooth formation was considered the signature developmental stage for the age. The relationship of the third molar occlusal surfaces with occlusal tables on the radiographs were checked and compared with the findings recorded during intra oral examination. RESULTS: Comparison with the London atlas shows that at age 9.5 years, the canine and premolar emergence are at least one year ahead and the third molar formation completes four years earlier in the WITS Atlas. DISCUSSION: Similarities in advancement in tooth formation and emergence across sub-Saharan Africa suggest that the WITS Atlas can be used for those populations as well.

Trajectory analysis among African hominoids can provide insights into genetic and epigenetic influences during ontogeny.

OBJECTIVES: Prior examination of the ontogeny of Hominoid talo-crural joint morphology using Singular Warp analysis suggested both a genetic and epigenetic signal during development. This question is examined using trajectory analysis and its implications for the Hominin fossil record explored. MATERIALS AND METHODS: Trajectory analysis was used to examine talo-crural joint shape at different molar eruption stages during development among a cohort of 221 specimens of Homo sapiens, Gorilla gorilla, Pan troglodytes, and Pan paniscus. Trajectory length, angle, and shape were compared among species. Trajectories that showed a consistent pattern of shape change were predicted to show a genetic signal, while change in that pattern an epigenetic signal. RESULTS: The trajectories of all four hominoid tali were consistent during M1-M2 development, but there was a change in Pan paniscus alone at M2-M3. The tibial trajectories were again consistent in M1-M2 development, however, only Pan paniscus persisted in this trajectory at M2-M3 while the other three changed. DISCUSSION: Trajectory analysis demonstrated an epigenetic signal in Pan paniscus in the talus and among the other three hominoids in the tibia. Behavioral (epigenetic) changes may impact hominoid ankle shape in extant species. These changes may reflect differences in locomotor repertoire altering shape, as has been suggested in the Hominin fossil record. Further examination of closely related hominoid species may provide insights into potential behavioral influences in the rapid change and diversity of Hominin talo-crural shape in the Plio-pleistocene.