Journal of dental research最新文献

This study aimed to compare the clinical effectiveness of resin-based fissure sealants (FS) and fluoride varnish (FV) in children at high caries risk. A practice-based split-mouth randomized clinical trial was conducted at 9 Public Dental Service (PDS) clinics in Norway. In total, 409 children age 6 to 10 y at high caries risk (d₃mft > 0) meeting inclusion criteria were recruited by dentists and dental hygienists during routine examination. Eligibility criteria were 2 fully erupted first permanent molars (FPMs) in the same jaw, with sound occlusal surfaces or with initial caries. Participation was voluntary, caregivers and eligible children were informed about the study, and written parental consent was obtained. FS and FV were randomly applied on contralateral FPMs in the same jaw, with each participant serving as their own control. FS was applied at baseline and thereafter maintained according to clinicians' conventional procedures, whereas FV was applied at baseline, 6 mo, and 12 mo. The study outcome was success, with no need for invasive treatment (caries control), while failure was defined as dentin carious lesion or restoration. Two-level mixed-effects logistic regression analysis was used to compare FS and FV groups. Of 409 recruited children, 369 (90%) children/tooth pairs were examined after 36 mo. Intention-to-treat analysis showed 94.1% adjusted predicted probability (^aPP) of success (95% confidence interval [CI] 91.7 to 96.4) in the FS group and 89.6% ^aPP (95% CI 86.5 to 92.7) in the FV group. In the adjusted analysis, the FV group had a lower OR for success compared with the FS group (OR 0.54, 95% CI 0.24 to 0.87). In the population studied, the clinical effectiveness of FS was statistically significantly higher compared with FV but below the estimated minimal clinically important difference of 10%.

Although mesenchyme is essential for inducing the epithelium of ectodermal organs, its precise role in organ-specific epithelial fate determination remains poorly understood. To elucidate the roles of tissue interactions in cellular differentiation, we performed single-cell RNA sequencing and imaging analyses on recombined tissues, where mesenchyme and epithelium were switched ex vivo between two types of embryonic mouse salivary glands: the parotid gland (a serous gland) and the submandibular gland (a predominantly mucous gland). We found partial induction of molecules that define gland-specific acinar and myoepithelial cells in recombined salivary epithelium. The parotid epithelium recombined with submandibular mesenchyme began to express mucous acinar genes not intrinsic to the parotid gland. While myoepithelial cells do not normally line parotid acini, newly induced myoepithelial cells densely populated recombined parotid acini. However, mucous acinar and myoepithelial markers continued to be expressed in submandibular epithelial cells recombined with parotid mesenchyme. Consequently, some epithelial cells appeared to be plastic, such that their fate could still be modified in response to mesenchymal signaling, whereas other epithelial cells appeared to be already committed to a specific fate. We also discovered evidence for bidirectional induction: transcriptional changes were observed not only in the epithelium but also in the mesenchyme after heterotypic tissue recombination. For example, parotid epithelium induced the expression of muscle-related genes in submandibular fibroblasts that began to mimic parotid fibroblast gene expression. These studies provide the first comprehensive unbiased molecular characterization of tissue recombination approaches exploring the regulation of cell fate.

Most of the elderly population is afflicted by periodontal diseases, creating a health burden worldwide. Cellular senescence is one of the hallmarks of aging and associated with several chronic comorbidities. Senescent cells produce a variety of deleterious secretions, collectively termed the senescence-associated secretory phenotype (SASP). This disrupts neighboring cells, leading to further senescence propagation and inciting chronic inflammation, known as "inflammaging." Detrimental repercussions within the tissue microenvironment can trigger senescence at a younger age, accelerate biological aging, and drive the initiation or progression of diseases. Here, we investigated the biological signatures of senescence in healthy and diseased gingival tissues by assessing the levels of key senescence markers (p16, lipofuscin, and β-galactosidase) and inflammatory mediators (interleukin [IL]-1β, IL-6, IL-8, matrix metalloproteinase [MMP]-1, MMP-3, and tumor necrosis factor-α). Our results showed significantly increased senescence features including p16, lipofuscin, and β-galactosidase in both epithelial and connective tissues of periodontitis patients compared with healthy sites in all age groups, indicating that an inflammatory microenvironment can trigger senescence-like alterations in younger diseased gingival tissues as well. Subsequent analyses using double staining with specific cell markers noted the enrichment of β-galactosidase in fibroblasts and macrophages. Concurrently, inflammatory mediators consistent with SASP were increased in the gingival biopsies obtained from periodontitis lesions. Together, our findings provide the first clinical report revealing susceptibility to elevated senescence and inflammatory milieu consistent with senescence secretome in gingival tissues, thus introducing senescence as one of the drivers of pathological events in the oral mucosa and a novel strategy for targeted interventions.

N6-methyladenosine (m⁶A) modification, a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), plays a pivotal role in stem cell fate determination. Calvarial bone development and maintenance are orchestrated by the cranial sutures. Cathepsin K (CTSK)-positive calvarial stem cells (CSCs) contribute to mice calvarial ossification. However, the role of m⁶A modification in regulating Ctsk⁺ lineage cells during calvarial development remains elusive. Here, we showed that METTL3 was colocalized with cranial nonosteoclastic Ctsk⁺ lineage cells, which were also associated with GLI1 expression. During neonatal development, depletion of Mettl3 in the Ctsk⁺ lineage cells delayed suture formation and decreased mineralization. During adulthood maintenance, loss of Mettl3 in the Ctsk⁺ lineage cells impaired calvarial bone formation, which was featured by the increased bone porosity, enhanced bone marrow cavity, and decreased number of osteocytes with the less-developed cellular outline. The analysis of methylated RNA immunoprecipitation sequencing and RNA sequencing data indicated that loss of METTL3 reduced Hedgehog (Hh) signaling pathway. Restoration of Hh signaling pathway by crossing Sufu^fl/+ alleles or by local administration of SAG21 partially rescued the abnormity. Our data indicate that METTL3 modulates Ctsk⁺ lineage cells supporting calvarial bone formation by regulating the Hh signaling pathway, providing new insights for clinical treatment of skull vault osseous diseases.

The increasing application of virtual surgical planning (VSP) in orthognathic surgery implies a critical need for accurate prediction of facial and skeletal shapes. The craniofacial relationship in patients with dentofacial deformities is still not understood, and transformations between facial and skeletal shapes remain a challenging task due to intricate anatomical structures and nonlinear relationships between the facial soft tissue and bones. In this study, a novel bidirectional 3-dimensional (3D) deep learning framework, named P2P-ConvGC, was developed and validated based on a large-scale data set for accurate subject-specific transformations between facial and skeletal shapes. Specifically, the 2-stage point-sampling strategy was used to generate multiple nonoverlapping point subsets to represent high-resolution facial and skeletal shapes. Facial and skeletal point subsets were separately input into the prediction system to predict the corresponding skeletal and facial point subsets via the skeletal prediction subnetwork and facial prediction subnetwork. For quantitative evaluation, the accuracy was calculated with shape errors and landmark errors between the predicted skeleton or face with corresponding ground truths. The shape error was calculated by comparing the predicted point sets with the ground truths, with P2P-ConvGC outperforming existing state-of-the-art algorithms including P2P-Net, P2P-ASNL, and P2P-Conv. The total landmark errors (Euclidean distances of craniomaxillofacial landmarks) of P2P-ConvGC in the upper skull, mandible, and facial soft tissues were 1.964 ± 0.904 mm, 2.398 ± 1.174 mm, and 2.226 ± 0.774 mm, respectively. Furthermore, the clinical feasibility of the bidirectional model was validated using a clinical cohort. The result demonstrated its prediction ability with average surface deviation errors of 0.895 ± 0.175 mm for facial prediction and 0.906 ± 0.082 mm for skeletal prediction. To conclude, our proposed model achieved good performance on the subject-specific prediction of facial and skeletal shapes and showed clinical application potential in postoperative facial prediction and VSP for orthognathic surgery.

Digital technology has emerged as a transformative tool in dental implantation, profoundly enhancing accuracy and effectiveness across multiple facets, such as diagnosis, preoperative treatment planning, surgical procedures, and restoration delivery. The multiple integration of radiographic data and intraoral data, sometimes with facial scan data or electronic facebow through virtual planning software, enables comprehensive 3-dimensional visualization of the hard and soft tissue and the position of future restoration, resulting in heightened diagnostic precision. In virtual surgery design, the incorporation of both prosthetic arrangement and individual anatomical details enables the virtual execution of critical procedures (e.g., implant placement, extended applications, etc.) through analysis of cross-sectional images and the reconstruction of 3-dimensional surface models. After verification, the utilization of digital technology including templates, navigation, combined techniques, and implant robots achieved seamless transfer of the virtual treatment plan to the actual surgical sites, ultimately leading to enhanced surgical outcomes with highly improved accuracy. In restoration delivery, digital techniques for impression, shade matching, and prosthesis fabrication have advanced, enabling seamless digital data conversion and efficient communication among clinicians and technicians. Compared with clinical medicine, artificial intelligence (AI) technology in dental implantology primarily focuses on diagnosis and prediction. AI-supported preoperative planning and surgery remain in developmental phases, impeded by the complexity of clinical cases and ethical considerations, thereby constraining widespread adoption.

A ligature-induced periodontitis model was established in wild-type and CD146^CreERT2; Rosa^tdTomato mice to explore the function of pericytes in alveolar bone formation. We found that during periodontitis progression and periodontal wound healing, CD146⁺/NG2⁺ pericytes were enriched in the periodontal tissue areas, which could migrate to the alveolar bone surface and colocalize with ALP⁺/OCN⁺ osteoblasts. Chemokine C-X-C motif receptor 4 (CXCR4) inhibition using AMD3100 blocked CD146-Cre⁺ pericyte migration and osteogenesis, as well as further exacerbated periodontitis-associated bone loss. Next, primary pericytes were sorted out by magnetic-activated cell sorting and demonstrated that C-X-C motif chemokine ligand 12 (CXCL12) promotes pericyte migration and osteogenesis via CXCL12-CXCR4-Rac1 signaling. Finally, the local administration of an adeno-associated virus for Rac1 overexpression in NG2⁺ pericytes promotes osteoblast differentiation of pericytes and increases alveolar bone volume in periodontitis. Thus, our results provided the evidence that pericytes may migrate and osteogenesis via the CXCL12-CXCR4-Rac1 axis during the pathological process of periodontitis.