OBJECTIVE: This systematic review summarizes the current knowledge on the association between the oral microbiota and dental caries in adolescents.
METHODS: An electronic search was carried out across five databases. Studies were included if they conducted research on generally healthy adolescents, applied molecular-based microbiological analyses and assessed caries status. Data extraction was performed by two reviewers and the Newcastle-Ottawa Scale was applied for quality assessment.
RESULTS: In total, 3935 records were reviewed which resulted in a selection of 20 cross-sectional studies (published 2005-2022) with a sample size ranging from 11 to 614 participants including adolescents between 11 and 19 years. The studies analyzed saliva, dental biofilm or tongue swabs with Checkerboard DNA-DNA hybridization, (q)PCR or Next-Generation Sequencing methods. Prevotella denticola, Scardoviae Wiggsiae, Streptococcus sobrinus and Streptococcus mutans were the most frequently reported species presenting higher abundance in adolescents with caries. The majority of the studies reported that the microbial diversity was similar between participants with and without dental caries.
CONCLUSIONS: This systematic review is the first that shows how the oral microbiota composition in adolescents appears to differ between those with and without dental caries, suggesting certain taxa may be associated with increased caries risk. However, there is a need to replicate and expand these findings in larger, longitudinal studies that also focus on caries severity and take adolescent-specific factors into account.

OBJECTIVE: Tooth agenesis (TA) is among the most common malformations in humans. Although several causative mutations have been described, the genetic cause often remains elusive. Here, we test whether whole genome sequencing (WGS) could bridge this diagnostic gap.
METHODS: In four families with TA, we assessed the dental phenotype using the Tooth Agenesis Code after intraoral examination and radiographic and photographic documentation. We performed WGS of index patients and subsequent segregation analysis.
RESULTS: We identified two variants of uncertain significance (a potential splice variant in PTH1R, and a 2.1 kb deletion abrogating a non-coding element in FGF7) and three pathogenic variants: a novel frameshift in the final exon of PITX2, a novel deletion in PAX9, and a known nonsense variant in WNT10A. Notably, the FGF7 variant was found in the patient, also featuring the WNT10A variant. While mutations in PITX2 are known to cause Axenfeld-Rieger syndrome 1 (ARS1) predominantly featuring ocular findings, accompanied by dental malformations, we found the PITX2 frameshift in a family with predominantly dental and varying ocular findings.
CONCLUSIONS: Severe TA predicts a genetic cause identifiable by WGS. Final exon PITX2 frameshifts can cause a predominantly dental form of ARS1.

Evidence suggests that dental caries is associated with chronic and acute malnutrition, manifested as stunting and wasting in children. However, studies have not always appropriately accounted for confounding factors or for the temporal ordering between exposure and outcome. This study examined relationships between the development of caries lesions with subsequent stunting and wasting outcomes using data from a population-based cohort in Cambodia. Caries incidence was assessed based on the presence of a new cavitated carious lesion or a new pulpally involved lesion across a 6-mo observation period. Anthropometric measurements were taken at regular intervals. Effects of carious lesions on stunting and wasting were assessed using inverse probability treatment weighting, adjusting for potential confounders, using z scores for height-for-age (HAZ) and weight-for-height (WHZ) as outcomes. In total, 894 children (mean age 20 mo at baseline) were followed over 2 y. At baseline, 350 (39.1%) were identified as having stunting malnutrition. At follow-up, 58 (6.5%) had a new pulpally involved lesion. There was no association between incidence of cavitated or pulpally involved carious lesions at follow-up and stunting (relative risk [RR] = 1.06; 95% confidence interval [CI]: 0.75, 1.50). The incidence of pulpally involved carious lesions had an effect on wasting prevalence (WHZ <-2; RR = 1.35; 95% CI: 0.70, 2.62) and WHZ scores (average treatment effect = -0.294; 95% CI: -0.538, -0.050). This study offers evidence that the development of pulpally involved carious lesions has an effect on WHZ scores. Oral health promotion and clinical prevention and management of dental caries should be explored as interventions to promote normal growth and development among preschool children, particularly in low-income settings.

The cranial base contains a special type of growth plate termed the synchondrosis, which functions as the growth center of the skull. The synchondrosis is composed of bidirectional opposite-facing layers of resting, proliferating, and hypertrophic chondrocytes, and lacks the secondary ossification center. In long bones, the resting zone of the epiphyseal growth plate houses a population of parathyroid hormone-related protein (PTHrP)-expressing chondrocytes that contribute to the formation of columnar chondrocytes. Whether PTHrP+ chondrocytes in the synchondrosis possess similar functions remains undefined. Using Pthrp-mCherry knock-in mice, we found that PTHrP+ chondrocytes predominantly occupied the lateral wedge-shaped area of the synchondrosis, unlike those in the femoral growth plate that reside in the resting zone within the epiphysis. In vivo cell-lineage analyses using a tamoxifen-inducible Pthrp-creER line revealed that PTHrP+ chondrocytes failed to establish columnar chondrocytes in the synchondrosis. Therefore, PTHrP+ chondrocytes in the synchondrosis do not possess column-forming capabilities, unlike those in the resting zone of the long bone growth plate. These findings support the importance of the secondary ossification center within the long bone epiphysis in establishing the stem cell niche for PTHrP+ chondrocytes, the absence of which may explain the lack of column-forming capabilities of PTHrP+ chondrocytes in the cranial base synchondrosis.

OBJECTIVE: This study aimed to determine the effect of C-type natriuretic peptide (CNP) overexpression on craniofacial growth during the pubertal growth period in mice.
METHODS: Six-week-old C57BL/6 mice were injected with pLIVE-Empty vectors (Control mice) and pLIVE-NPPC vectors (CNP mice) using the hydrodynamic method. Morphological analyses were performed at the age of 12 weeks.
RESULTS: Micro-computed tomography (µCT) images showed significant (p < 0.05) hyperplasia in the maxilla along the sagittal plane (CNP mice: 13.754 mm, Control mice: 13.215 mm). Further, the images revealed significant bone overgrowth in the sagittal direction in the sphenoid (CNP mice: 6.936 mm, Control mice: 6.411 mm) and occipital (CNP mice: 4.051 mm, Control mice: 3.784 mm) bones in the CNP mice compared with that in the Control mice. Compared with SAP-Nppc-Tg mice in previous studies, although there was no effect on nose length and nasal bone length, the effect was sufficient to improve craniofacial hypogrowth. Furthermore, CNP promoted sagittal cranial growth by increasing the thickness of the spheno-occipital synchondrosis in organ cultures and nasal septal cartilage in micromass cultures, which were derived from 6-week-old mice.
CONCLUSIONS: We have previously shown that the elevated blood levels of CNP from the neonatal period affect midfacial skeletogenesis by promoting endochondral ossification using mice (SAP-Nppc-Tg mice). The overexpression of CNP, even in 6-weeks-old mice, promoted growth in the sagittal direction within the maxillary region. These findings indicate the therapeutic potential of CNP for the treatment of midfacial hypoplasia during the pubertal growth spurt.

One of the most common dental anomalies in humans is the congenital absence of teeth, referred to as tooth agenesis. The association of tooth agenesis to craniofacial morphology has been previously investigated but remains unclear. We investigated this association by applying geometric morphometric methods in a large sample of modern humans. In line with previous studies, we report here that a reduced teeth number is linked to a less convex profile, as well as to a shorter face. The effects were similar for males and females; they increased as the severity of the tooth agenesis increased and remained unaltered by the inclusion of third molars and of allometry in the analysis. Furthermore, in cases with tooth agenesis only in the maxilla, there was no detectable effect in mandibular shape, whereas maxillary shape was affected independently of the location of missing teeth. The robustness of the present sample along with the shape analysis and the statistical approach applied, allowed for thorough testing of various contributing factors regarding the presence but also the magnitude of effects. The present findings suggest a relationship between number of teeth and overall craniofacial development and have evolutionary implications.

UNASSIGNED: Oral microbiota that established in the early years of life may influence the child\'s oral health in the long term. Until now, no consensus is reached about whether the development of the oral microbiota is more related with age increase or more with teeth eruption.
UNASSIGNED: To analyze the microbiota development of both saliva and supragingival plaque during the gradual eruption of primary teeth in caries-free infants and toddlers.
UNASSIGNED: Saliva and plaque samples were collected at five and four dentition states, respectively, and were identified by bacterial 16S rRNA gene sequencing.
UNASSIGNED: During the longitudinal observation, the saliva ecosystem seemed more complex and dynamic than the plaque, with larger bacteria quantity and more significantly varied species over time. About 70% of the initial colonized OTUs in plaque persisted until the completion of the primary dentition. Transient bacteria were mostly detected in the early saliva and plaque microbiota, which came from the environment and other sites of the human body. Microbial diversity in both saliva and plaque varied greatly from pre-dentition to full eruption of eight anterior teeth, but not during the eruption of primary molars.
UNASSIGNED: Oral bacterial development follows an ordered sequence during the primary teeth eruption. \'Fully eruption of all primary anterior teeth\' is a critical stage in this process.

OBJECTIVE: To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial proportions of a Dutch control group.
METHODS: We included seventy-four patients (43 patients with Muenke syndrome, 22 patients with Saethre-Chotzen syndrome, and 9 patients with TCF12-related craniosynostosis) who were referred between 1990 and 2020 (age range 4.84 to 16.83 years) and were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children\'s Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands. The control group consisted of 208 healthy children.
RESULTS: Cephalometric values comprising the midface were decreased in Muenke syndrome (ANB: β = -1.87, p = 0.001; and PC1: p < 0,001), Saethre-Chotzen syndrome (ANB: β = -1.76, p = 0.001; and PC1: p < 0.001), and TCF12-related craniosynostosis (ANB: β = -1.70, p = 0.015; and PC1: p < 0.033).
CONCLUSIONS: In this study, we showed that the midface is hypoplastic in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis compared to the Dutch control group. Furthermore, the rotation of the maxilla and the typical craniofacial buildup is significantly different in these three craniosynostosis syndromes compared to the controls.
CONCLUSIONS: The maxillary growth in patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is impaired, leading to a deviant dental development. Therefore, timely orthodontic follow-up is recommended. In order to increase expertise and support treatment planning by medical and dental specialists for these patients, and also because of the specific differences between the syndromes, we recommend the management of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis in specialized multidisciplinary teams.

N6-methyladenosine (m6A) is a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), which is involved in various developmental and disease processes. However, the connection between the epigenetic modification of m6A and glucose metabolism during osteogenesis is still unclear. Here, we show that interference with METTL3 in dental pulp stem cells (DPSCs) inhibits cell proliferation and osteogenic differentiation. Moreover, transcriptome sequencing and metabolic testing were used to explore the mechanism between glucose metabolism and m6A modification in METTL3-knockdown DPSCs. Methylated RNA immunoprecipitation-quantitative polymerase chain reaction and RNA stability assays were used to determine the target genes of METTL3. Mechanistically, METTL3 directly interacts with ATP citrate lyase (ACLY) and a mitochondrial citrate transporter (SLC25A1) and then further affects the glycolytic pathway. M6A-mediated ACLY and SLC25A1 stability depends on the m6A readers IGF2BP2 and IGF2BP2/3, respectively. Our experiments uncovered the potential molecular mechanism of epigenetic modification in osteogenic differentiation, providing new ideas for the clinical application of stem cells and the intervention of metabolic bone diseases.

BACKGROUND: Research shows that successfully transitioning from intermediate school to secondary school is pivotal for students to remain on track to graduate. Studies also indicate that a successful transition is a function not only of how prepared the students are academically but also whether they have the social-emotional learning (SEL) skills to succeed in a more independent secondary school environment.
OBJECTIVE: Yet, little is known about whether students\' SEL skills are stable over time, and if they are not, whether a student\'s initial level of SEL skills at the start of intermediate school or change in SEL skills over time is a better indicator of whether the student will be off track academically in 9th grade. This study begins to investigate this issue.
METHODS: We use four years of longitudinal SEL data from students in a large urban district with a sample size of ˜3,000 students per timepoint.
METHODS: We use several years of longitudinal SEL data to fit growth models for three constructs shown to be related to successfully transitioning to secondary school. In so doing, we examine whether a student\'s mean SEL score in 6th grade (status) or growth between 6th and 8th grade is more predictive of being off track academically in 9th grade.
RESULTS: Results indicate that, while status is more frequently significant, growth for self-management is also predictive above and beyond status on that construct.
CONCLUSIONS: Findings suggest that understanding how a student develops social-emotionally can improve identification of students not on track to succeed in high school.