Journal of dental research最新文献

Candida albicans has been implicated as a potential cariogenic microorganism, yet no prospective longitudinal studies have examined its role in severe early childhood caries (S-ECC). This study aimed to evaluate the association between oral C. albicans and the onset of S-ECC in a longitudinal setting. This prospective birth cohort study (2018 to 2023) enrolled 186 low-income pregnant women in their third trimester in Western New York, United States. Overall, 160 eligible infants born to these women were followed from birth to 2 y at 7 time points. Oral samples were collected to assess Candida species (C. albicans, Candida krusei, and Candida glabrata) and Streptococcus mutans. The primary outcome was the onset of S-ECC. Two-step LASSO (least absolute shrinkage and selection operator)-penalized logistic regression models were developed to identify predictive factors for S-ECC from 234 covariates grouped by their proximal association with S-ECC: infant oral microorganisms, biological-environmental factors, and maternal characteristics. Logistic regression was used to validate the association between C. albicans and S-ECC. Among the 118 children who completed the study, 28% developed S-ECC. The racial background of the cohort was 57% Black, 21% White, and 22% other. Oral C. albicans colonized in 12% of infants at 1 wk, peaking at 57% by 18 mo. Salivary C. albicans was associated with a 4.47-fold increased risk for S-ECC (odds ratio [OR]; 95% CI, 1.28 to 15.58; P = 0.02), in addition to other risk factors, including plaque score (OR, 5.19; 95% CI, 2.10 to 12.83) and salivary S. mutans (OR, 9.74; 95% CI, 2.27 to 41.79). C. albicans demonstrated strong time sensitivity in predicting S-ECC as early as 1 mo, contrasting with S. mutans, which exhibited predictive ability after 1 y. Oral C. albicans could serve as a novel biological marker for predicting ECC risk in infancy, shining a light on opportunities to develop innovative caries-predictive and preventive strategies targeting fungal contributions in pediatric care settings.

The clinical classification of ameloblastoma (AM) plays a decisive role in the selection of treatment options, but the difference of single-cell landscape among clinical classifications is still unclear. At the same time, there is an urgent need to understand the key cell subtypes that determine the clinical subtypes. We characterized the single-cell transcriptional profiles of clinical subtypes of AM. We also characterized a pseudotime transition trajectory from immunoactive epithelial cells to vascular-associated fibroblasts, identifying key transcription factors involved in this process. Notably, we observed significant heterogeneity between M1 and M2 macrophages among the clinical subtypes of AM. Furthermore, our analysis revealed that metabolic disorder in AM was primarily driven by the metabolic disturbances in M1 and M2 macrophages. At the cellular communication level, we highlighted the role of M2 macrophages in mediating cell interactions, focusing on the RANKL/RANK pathway associated with osteoclast activity. Finally, we attempted to establish a unicystic AM-derived epithelial cell line and utilized it to construct an AM-like organoid model; we found that M2 macrophages competed with AM for L-cysteine to achieve cystic changes in the solid lesion. Our exploration of pathogenesis underlying various clinical types of AM advances our knowledge of AM heterogeneity, offering promising targets for novel therapeutic strategies.

Perineural invasion (PNI) frequently occurs in head and neck squamous cell carcinoma (HNSCC), which correlates with poor survival and induces intractable pain and numbness. There is no effective treatment for PNI or associated pain. To gain a better understanding of PNI at the molecular and cellular level, we produced an orthotopic, syngeneic mouse model of PNI by inoculating mouse oral cancer cells into the infraorbital nerve (ION), a nerve that is susceptible to cancer invasion in patients with HNSCC. Mice with PNI in the ION exhibited both evoked and spontaneous nociception and impaired oral function, mimicking human conditions. PNI resulted in a drastic reduction in the proportion and altered mechanical thresholds in mechanically sensitive trigeminal neurons; axon and myelin abnormalities, as well as phagocytic cells, were observed. The tumor bed is marked by CD4⁺ and CD8⁺ T cells, CD68⁺ cells, and F4/80⁺ macrophages, while CD4⁺, CD8⁺, and CD68⁺ immune cells can be found surrounding the nerve. The intraneural niche is predominantly marked by CD68 that does not overlap with F4/80 but instead overlaps with NF200 and MPZ and occasionally with DAPI, suggesting these are likely phagocytic macrophages or Schwann cells. Finally, our RNA sequencing pathway analysis in mouse and human HNSCC found perturbed pathways in neuroinflammation, mitochondrial dysfunction, and cellular metabolism. Additionally, ION-PNI exhibits nerve degenerative features with perturbed pathways that are observed in Alzheimer, Parkinson, and prion diseases. In conclusion, we report a novel, anatomically relevant in vivo model that could be used to study the cellular and molecular mechanisms of PNI-induced neuropathies. Importantly, we found that PNI resembles neurodegenerative diseases with features of altered sensory transduction and conduction, neuroinflammation, and mitochondrial dysfunction, which may underlie peripheral neuropathies, such as pain.

The development of craniofacial bones and teeth relies heavily on the Wnt signaling pathway, yet the specific mechanisms and Wnt variants involved remain under continual investigation. Using publicly available single-cell sequencing data from the mouse incisor, we reveal Wnt1 expression across dental structures and investigate its role using a Col1a1-dependent Wnt1 transgenic mouse model. Inducing Wnt1 early on affects craniofacial bone without disturbing tooth development, but prolonged embryonic induction leads to postnatal mortality with osteopetrosis-like bone overgrowth and malformed teeth. While tooth formation was initially unaffected by postnatal Wnt1 induction, prolonged activation impaired tooth root formation and odontoblast differentiation, resulting in shortened roots and thinner dentin. Three-dimensional micro-computed tomography quantification reveal that both embryonic and postnatal activation of Wnt1 significantly increase neural crest-derived craniofacial bone volume, whereas mesenchymal-derived craniofacial bones are unaffected. Importantly, osteoclastogenesis is suppressed by Wnt1 in a dose-dependent manner, revealed through bulk RNA sequencing and in vitro experiments. These findings emphasize the differential effects of Wnt1 on bone development based on origin and highlight its role in modulating osteoclast activity, indicating broader implications for craniofacial development and potential therapeutic avenues.

The molecular mechanisms mediating barrier functions of the junctional epithelium (JE) are incompletely understood. The aim of this study was to gain mechanistic insights into how reduced Wnt/β-catenin signaling affects the metabolism, turnover, and attachment of JE cells to the tooth surface. A membrane-permeable selective inhibitor of the Wntless protein, C59, was topically delivered to the JE. Wnt pathway suppression was verified by using Axin2^LacZ/+ and Axin2Cre^ERT2/+;R26R^mTmG/+ strains of mice. Quantitative analyses were carried out at multiple time points to assess mitotic activity, apoptosis, expression of hemidesmosomal attachment proteins, distribution of immune cells, collagen remodeling, and alveolar bone resorption. To complement these studies, Wntless was genetically deleted in osteocalcin-expressing cells, including those in the JE, after which the same quantitative analyses were performed. C59 caused a dose-dependent inhibition in Wnt signaling, which led to reduced mitotic activity and increased apoptosis in the JE. Continued dosing of C59 was accompanied by downregulation of the hemidesmosome attachment proteins laminin 5, plectin, and integrin β4 and a disruption in collagen orientation. A genetic approach in which Wntless function was inhibited in osteocalcin-expressing JE cells yielded similar inhibitory effects on Wnt signaling, mitotic activity, the JE's attachment to the tooth surface, and an increase in immune cells within the connective tissue. Wnt/β-catenin signaling is required for JE homeostasis, and disruptions to the pathway are sufficient to cause JE breakdown and attachment loss. Methods to modulate Wnt/β-catenin signaling may prove beneficial in restoring JE homeostasis after injury or disease.

The gradual phaseout of dental amalgam has contributed to a significant increase in the use of resin-based materials. While these materials offer several desirable properties, concerns persist regarding their biocompatibility, particularly the release of bisphenol A (BPA). BPA is an endocrine-disrupting chemical linked to adverse effects on human health, including reproductive, developmental, and metabolic disorders. Although food contact materials are the primary source of human BPA exposure and the contribution of dental materials is minor, the associated risks cannot be dismissed due to BPA's nonmonotonic dose-response relationship. In 2023, the European Food Safety Authority proposed a 20,000-fold reduction in the tolerable daily intake of BPA to 0.2 ng/kg body weight, citing immune system effects at extremely low doses. This proposal has sparked regulatory and scientific debate, as adopting such a stringent limit would effectively ban the use of BPA in food contact materials and many other products. Given this context, it is essential to assess the release of BPA from dental materials both in vitro and in vivo. However, data interpretation is complicated by methodological inconsistencies, including variations in material composition, specimen preparation, choice of extraction media, experimental duration, and analytical methods. In addition, pivotal differences in reporting results make it difficult to synthesize findings and draw reliable conclusions. This review examines the controversy surrounding BPA, critically evaluates evidence on its release from dental materials, and explores mitigation strategies. By highlighting gaps in knowledge and proposing future research directions, this review aims to provide clinicians, researchers, and policymakers with a clearer understanding of BPA-related complexities, ultimately contributing to patient safety and material innovation.

Fibroblasts isolated from discarded lip tissue obtained during cheiloplasty in patients with cleft lip/palate (CLP) show promising osteogenic potential and may be an appealing cell source for autologous bone regeneration. As the lip is a mucocutaneous junction, explant cultures from unseparated lip biopsies produce mesenchymal outgrowths composed of skin- and mucosa-derived fibroblasts. The proportions of the 2 fibroblast populations, however, differ among CLP patients and depend on the morphology of the excised sample, which is unique for each donor. Understanding the osteogenic activities of CLP fibroblast populations with varying skin-to-mucosa ratios is critical for their therapeutic application. We isolated CLP fibroblasts from 10 unseparated lip biopsies and comprehensively evaluated them for their bone differentiation capacities in vitro, demonstrating heterogeneous osteogenic potentials. Because there are no markers that can distinguish skin from mucosa fibroblasts, we used the respective and matching CLP keratinocytes to ascertain the skin-to-mucosa ratio of the 10 specimens. Thus, we found that CLP fibroblasts isolated from biopsies with high skin-to-mucosa ratios had a much higher osteogenic capacity than those derived from biopsies with low skin-to-mucosa ratios. To validate and solidify these findings, we carefully separated skin and mucosa tissues during corrective lip surgery to isolate pure skin and mucosa CLP lip fibroblasts. Indeed, skin had a higher osteogenic potential than their mucosal counterparts did. Furthermore, we discovered that the high osteogenic activity in skin was limited to specific subpopulations of yet unknown identities. Our findings indicate that skin fibroblasts perform better than their mucosal counterparts do, even though both types of fibroblasts can differentiate into bone-forming cells.

Socioeconomic status (SES) measures one's access to social resources across various dimensions. Traditionally, studies on SES commonly use principal component analysis (PCA), a data-driven method, to condense these dimensions into components, typically selecting the first component to represent SES. However, PCA may lack specificity for particular outcomes. Decision tree analysis (DTA), a knowledge-driven approach that identifies outcome-specific dimensions, may address PCA's weaknesses but might not comprehensively capture SES. This study hypothesized that combining DTA and PCA to create SES predictors could enhance predictive accuracy more than using PCA alone could. It also explored whether the DTA-PCA combination, incorporating only significant loading indicators (SLIs) of the first component, could simplify SES predictors without compromising predictive accuracy. The study analyzed 12 SES indicators from the Study of Mothers' and Infants' Life Events Affecting Oral Health (SMILE) birth cohort study, involving 2,182 children. Five SES composites were created: 1 solely from DTA-identified indicators and 2 pairs combining values from either the entire first PCA component or SLIs with and without DTA. These composites served as predictors for predicting dental caries in 5 predictive models. Model accuracy was evaluated using root mean squared error with 5-fold cross-validation. SES composites derived from the DTA-PCA combination demonstrated superior predictive accuracy compared with those from the PCA-only approach. By incorporating only SLIs, this hybrid method generated SES predictors that not only outperformed those using the entire first component but also demonstrated noninferiority relative to the DTA-only method. This approach offers a promising framework for developing SES composites to predict dental caries, potentially improving the precision of predictive models. In addition, this method offers a practical framework for creating composite predictors from multi-item measurements across various outcomes. For future research using this method, a 3-step process is recommended: (1) identify relevant items using DTA, (2) determine their weights through PCA, and (3) generate a composite using the SLIs.