Journal of dental research最新文献

The prognosis and survival rate of head and neck squamous cell carcinoma (HNSCC) have remained unchanged for years, and the pathogenesis of HNSCC is still not fully understood, necessitating further research. An ideal animal model that accurately replicates the complex microenvironment of HNSCC is urgently needed. Among all the animal models for preclinical cancer research, tumor-bearing mouse models are the best known and widely used due to their high similarity to humans. Currently, mouse models for HNSCC can be broadly categorized into chemical-induced models, genetically engineered mouse models (GEMMs), and transplanted mouse models, each with its distinct advantages and limitations. In chemical-induced models, the carcinogen spontaneously initiates tumor formation through a multistep process. The resemblance of this model to human carcinogenesis renders it an ideal preclinical platform for studying HNSCC initiation and progression from precancerous lesions. The major drawback is that these models are time-consuming and, like human cancer, unpredictable in terms of timing, location, and number of lesions. GEMMs involve transgenic and knockout mice with gene modifications, leading to malignant transformation within a tumor microenvironment that recapitulates tumorigenesis in vivo, including their interaction with the immune system. However, most HNSCC GEMMs exhibit low tumor incidence and limited prognostic significance when translated to clinical studies. Transplanted mouse models are the most widely used in cancer research due to their consistency, availability, and efficiency. Based on the donor and recipient species matching, transplanted mouse models can be divided into xenografts and syngeneic models. In the latter, transplanted cells and host are from the same strain, making syngeneic models relevant to study functional immune system. In this review, we provide a comprehensive summary of the characteristics, establishment methods, and potential applications of these different HNSCC mouse models, aiming to assist researchers in choosing suitable animal models for their research.

Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in ENAM, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of ENAM, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of Enam on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)-related genes and TNFRSF10B, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 ENAM mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an ENAM mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for ENAM-associated AI.

Harold (Hal) C. Slavkin, DDS, the 22nd president of the American Association for Dental, Oral, and Craniofacial Research (1993 to 1994), died on December 22, 2023. During a career that spanned almost 6 decades, Hal distinguished himself as an international authority on craniofacial biology and an advocate for oral health equity. He served as dean of the University of Southern California's dental school, founded the school's Center for Craniofacial Molecular Biology, created the nation's first PhD program in craniofacial biology, and served as the sixth director of the National Institute of Dental and Craniofacial Research. Hal's studies of the molecular and cellular underpinnings of craniofacial malformations prepared him to champion translational research later in his career, when his work with patient advocates revealed the importance of applying new discoveries to clinical practice. A visionary thinker, skilled administrator, progressive educator, compelling communicator, researcher, scholar, and mentor, Hal was known as a Renaissance leader. He rejoiced in fostering collaborative synergies among people and organizations. Throughout his life, family was his central grounding force. He and his wife, Lois, advanced a wide range of social and community initiatives and took great pride in their children, grandchildren, and great-grandchildren. We remember Hal for his indelible spirit, unflappable enthusiasm for science, fierce advocacy for social justice, and infectious zest for life. Here, we outline his multidimensional accomplishments through the lenses of academia, government, and nonprofit organizations. Although it is with heavy hearts that we bid goodbye to this remarkable man, our spirits are lightened by the many gifts he left behind.

Periodontal tissue destruction in periodontitis is a consequence of the host inflammatory response to periodontal pathogens, which could be aggravated in the presence of type 2 diabetes mellitus (T2DM). Accumulating evidence highlights the intricate involvement of macrophage-mediated inflammation in the pathogenesis of periodontitis under both normal and T2DM conditions. However, the underlying mechanism remains elusive. Alpha-2-glycoprotein 1 (AZGP1), a glycoprotein featuring an MHC-I domain, has been implicated in both inflammation and metabolic disorders. In this study, we found that AZGP1 was primarily colocalized with macrophages in periodontitis tissues. AZGP1 was increased in periodontitis compared with controls, which was further elevated when accompanied by T2DM. Adeno-associated virus-mediated overexpression of Azgp1 in the periodontium significantly enhanced periodontal inflammation and alveolar bone loss, accompanied by elevated M1 macrophages and pyroptosis in murine models of periodontitis and T2DM-associated periodontitis, while Azgp1^-/- mice exhibited opposite effects. In primary bone marrow-derived macrophages stimulated by lipopolysaccharide (LPS) or LPS and palmitic acid (PA), overexpression or knockout of Azgp1 markedly upregulated or suppressed, respectively, the expression of macrophage M1 markers and key components of the NLR Family Pyrin Domain Containing 3 (NLRP3)/caspase-1 signaling. Moreover, conditioned medium from Azgp1-overexpressed macrophages under LPS or LPS+PA stimulation induced higher inflammatory activation and lower osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs). Furthermore, elevated M1 polarization and pyroptosis in macrophages and associated detrimental effects on hPDLSCs induced by Azgp1 overexpression could be rescued by NLRP3 or caspase-1 inhibition. Collectively, our study elucidated that AZGP1 could aggravate periodontitis by promoting macrophage M1 polarization and pyroptosis through the NLRP3/casapse-1 pathway, which was accentuated in T2DM-associated periodontitis. This finding deepens the understanding of AZGP1 in the pathogenesis of periodontitis and suggests AZGP1 as a crucial link mediating the adverse effects of diabetes on periodontal inflammation.

This study reviews and appraises the methodological and reporting quality of prediction models for tooth loss in periodontitis patients, including the use of regression and machine learning models. Studies involving prediction modeling for tooth loss in periodontitis patients were screened. A search was performed in MEDLINE via PubMed, Embase, and CENTRAL up to 12 February 2022, with citation chasing. Studies exploring model development or external validation studies for models assessing tooth loss in periodontitis patients for clinical use at any time point, with all prediction horizons in English, were considered. Studies were excluded if models were not developed for use in periodontitis patients, were not developed or validated on any data set, predicted outcomes other than tooth loss, or were prognostic factor studies. The CHARMS checklist was used for data extraction, TRIPOD to assess reporting quality, and PROBAST to assess the risk of bias. In total, 4,661 records were screened, and 45 studies were included. Only 26 studies reported any kind of performance measure. The median C-statistic reported was 0.671 (range, 0.57-0.97). All studies were at a high risk of bias due to inappropriate handling of missing data (96%), inappropriate evaluation of model performance (92%), and lack of accounting for model overfitting in evaluating model performance (68%). Many models predicting tooth loss in periodontitis are available, but studies evaluating these models are at a high risk of bias. Model performance measures are likely to be overly optimistic and might not be replicated in clinical use. While this review is unable to recommend any model for clinical practice, it has collated the existing models and their model performance at external validation and their associated sample sizes, which would be helpful to identify promising models for future external validation studies.

Dimethacrylate-based chemistries feature extensively as resin monomers in dental resin-based materials due to their distinguished overall performance. However, challenges endure, encompassing inadequate mechanical attributes, volumetric shrinkage, and estrogenicity. Herein, we first synthesized a novel resin monomer, 9-armed starburst polyurethane acrylate (NPUA), via the grafting-onto approach. Compared to the primary commercial dental monomer 2,2-bis [p-(2'-hydroxy-3'-methacryloxypropoxy) phenyl] propane (Bis-GMA) (with a viscosity of 1,174 ± 3 Pa·s and volumetric shrinkage of 4.7% ± 0.1%), the NPUA monomer achieves the lower viscosity (158 ± 1 Pa·s), volumetric shrinkage (2.5% ± 0.1%), and cytotoxicity (P < 0.05). The NPUA-based resins exhibit the higher flexural strength, flexural modulus, hardness, and hydrophobicity and lower volumetric shrinkage, water absorption, and solubility compared to the Bis-GMA (70 wt%)/TEGDMA (30 wt%) resins. The NPUA-based composites exhibit significantly higher flexural strength, flexural modulus, and hardness and lower volumetric shrinkage (171.4 ± 3.0 MPa, 12.6 ± 0.5 GPa, 2.0 ± 0.2 GPa, and 3.4% ± 0.2%, respectively) compared to the Bis-GMA group (120.3 ± 4.7 MPa, 9.4 ± 0.7 GPa, 1.5 ± 0.1 GPa, and 4.7% ± 0.2%, respectively; P < 0.05). This work presents a viable avenue for augmenting the physicochemical attributes of dental resins.

Existing studies on multimorbidity have largely excluded oral diseases in multimorbidity prevalence estimates. The reason behind this is somewhat unclear, as chronic oral conditions are highly prevalent, affecting over half the global population. To address this gap, we examined the relationship between social disadvantage and multimorbidity, stratifying by the inclusion and exclusion of oral conditions. For participants aged 30 y and over (n = 3,693), cross-sectional analysis was carried out using the US National Health and Nutrition Survey (2013-2014). Multimorbidity was defined as having 2 or more chronic conditions. Five medical conditions were examined: diabetes, asthma, arthritis, cardiovascular disease, and depression, as well as 4 oral health conditions: caries, periodontal disease, number of teeth, and edentulousness. Education and income poverty ratio were selected as measures of social disadvantage. Multimorbidity prevalence estimates according to social disadvantage were analyzed on an absolute and relative scale using inverse probability treatment weighting (IPTW), adjusting for age, sex, and ethnicity. The inclusion of oral health conditions in the assessment of multimorbidity increased the overall prevalence of multimorbidity from 20.8% to 53.4%. Findings from IPTW analysis demonstrated clear social gradients for multimorbidity estimates stratified by the exclusion of oral conditions. Upon inclusion of oral conditions, the prevalence of multimorbidity was higher across all social groups for both education and income. Stratifying by the inclusion of oral conditions, the mean probability of multimorbidity was 27% (95% confidence interval [CI], 23%-30%) higher in the low-education group compared to the high-education group. Similarly, the mean probability of multimorbidity was 44% (95% CI, 40%-48%) higher in the low-income group. On a relative scale, low education was associated with a 1.52 times (95% CI, 1.44-1.61) higher prevalence of multimorbidity compared to high education. Low income was associated with a 2.18 (95% CI, 1.99-2.39) higher prevalence of multimorbidity. This novel study strongly supports the impact of chronic oral conditions on multimorbidity prevalence estimates.

Analyses of National Health and Nutrition Examination Survey (NHANES) data suggested a significant decrease in sealant prevalence among children between 2011 to 2014 and 2015 to 2018. We explore whether this decrease could be associated with possible changes in 1) clinical sealant delivery, 2) dental materials (i.e., increased use of glass ionomer [GI] sealants resulting in an inability to detect sealant fragments that still provide preventive benefits or increased use of composite restorations leading to misclassifying sealants as restorations), and 3) examination sensitivity and specificity. We used NHANES data to estimate the prevalences of sealants, untreated caries, and restorations in ≥1 first permanent molar among children aged 7 to 10 y and used Medical Expenditure Panel Survey data to estimate the annual clinical delivery of sealants and fluoride treatments. We examined changes in outcomes between 2 periods (P < 0.05) controlling for selected sociodemographic characteristics. NHANES sealant examination quality was based on the reference examiner's replicate examinations. The adjusted prevalence of sealants decreased relatively by 27.5% (46.6% vs. 33.8%). Overall, untreated caries decreased. Untreated caries and restoration decreased among children without sealants. Annual clinical sealant delivery did not change, whereas fluoride treatment delivery increased. The decrease in sealant prevalence held when assessed for various age ranges and NHANES cycle combinations. While sealant examination specificity remained similar between the periods, sensitivity (weighted by the proportion of exams by each examiner) decreased relatively by 17.4% (0.92 vs. 0.76). These findings suggest that decreased sealant prevalence was not supported by decreased clinical sealant delivery nor increased use of composite restorations. Decreased examination sensitivity, which could be due to an increased use of GI sealants, could contribute to the decrease in sealant prevalence. The decrease in caries among children without sealants could suggest the increased use of GI sealants. However, we could not rule out that the decrease in caries could be attributable to increased fluoride treatment delivery.

Research on 3-dimensional (3D) printed porous zirconia-based dental implants is still in its infancy. This study aimed to evaluate the biological responses of novel zirconia implants with p-cell structures fabricated by 3D printing. The solid zirconia samples exhibited comparable density, 3-point flexural strength, and accelerated aging properties compared to specimens prepared previously by conventional methods. Cell-based experiments showed that the p-cell structure promoted cell proliferation, adhesion, and osteogenesis-related protein expression. Mechanical tests showed that both p-cell and control implants could withstand a torque of 35 Ncm without breaking. The mean maximum breaking loads of p-cell and control implants were 1,222.429 ± 115.591 N and 1,903.857 ± 250.673 N, respectively, which were much higher than the human physiological chewing force and human mean maximum occlusal force. An animal experiment showed that the bone trabeculae around the implants were significantly thicker, more numerous, and denser in the p-cell group than in the control group. This work could provide promising guidance for further exploring 3D printing techniques for porous zirconia bionic implants in dentistry.