Journal of dental research最新文献

{"title":"Targeting Epigenetic Dysregulations in Head and Neck Squamous Cell Carcinoma.","authors":"Y Li, C Lu","doi":"10.1177/00220345241297122","DOIUrl":"10.1177/00220345241297122","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is one of the deadliest human cancers, with the overall 5-year survival rate stagnating in recent decades due to the lack of innovative treatment approaches. Apart from the recently Food and Drug Administration-approved epidermal growth factor receptor inhibitor and immune checkpoint inhibitor, alternative therapeutic strategies that target epigenetic abnormalities, an emerging cancer hallmark, remain to be fully explored. A pathological epigenetic landscape, characterized by widespread reprogramming of chromatin modifications such as DNA methylation and histone modifications, which drives transcription deregulation and genome reorganization, has been extensively documented in numerous cancers, including HNSCC. Growing evidence indicates that these frequent epigenomic alterations play pivotal roles in regulating malignant transformation, promoting metastasis and invasion, and reshaping the tumor microenvironment. Furthermore, these epigenetic changes also present unique vulnerabilities that open new avenues for identifying novel prognostic biomarkers and developing targeted antitumor therapies. In this review, we summarize recent discoveries of epigenetic dysregulations in HNSCC, with a focus on deregulated chromatin modifications, which include aberrant DNA methylation, oncohistone H3 lysine 36 to methionine (H3K36M) mutation, as well as recurrent mutations or altered expression of chromatin-modifying enzymes such as NSD1, EZH2, and KMT2C/D. Importantly, we discuss the various molecular mechanisms underlying the contributions of these epigenetic alterations to HNSCC development, particularly their involvement in deregulated cell proliferation and cell death, metabolic reprogramming, tumor immune evasion, and phenotypic plasticity. Finally, we conclude by highlighting the translational and clinical implications of targeting the epigenetic machinery, which offers promising prospects for overcoming resistance to conventional radiotherapy/chemotherapy and enhancing the response to immunotherapy in HNSCC.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"225-234"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Childhood Exposures to Fluorides and Cognitive Neurodevelopment: A Population-Based Longitudinal Study.","authors":"L G Do, A Sawyer, A John Spencer, S Leary, J K Kuring, A L Jones, T Le, C E Reece, D H Ha","doi":"10.1177/00220345241299352","DOIUrl":"10.1177/00220345241299352","url":null,"abstract":"<p><p>It is important to maintain confidence in the risk and benefit balance of major caries-preventive programs using fluoride. The ongoing debate about potential effects of early-life exposures to fluoride on cognitive neurodevelopment requires high-quality scientific evidence. This study aimed to investigate the potential effects of fluoride exposure on cognitive neurodevelopment assessed with the Wechsler Adult Intelligence Scale 4th edition (WAIS-IV) in an Australian population-based sample. The sample was selected from the National Child Oral Health Study (NCOHS) 2012-2014. NCOHS collected data on socioeconomic factors, oral health behaviors, and residential history to estimate percentage lifetime exposure to fluoridated water during the first 5 y of life (%LEFW). NCOHS children were also examined by trained and calibrated examiners to assess dental fluorosis (a reliable and valid individual biomarker of total fluoride intake during early childhood). The sample was followed up in 2022-2023 to collect data on cognitive neurodevelopment (intelligence quotient [IQ]) using the WAIS-IV, which was administered by trained and calibrated qualified psychologists. Multivariable regression models were generated to investigate associations between the 2 exposure measurements (%LEFW and dental fluorosis) with full-scale IQ (FSIQ) scores, controlling for important confounding effects. Hypotheses of noninferiority were also tested, contrasting different levels of exposure to fluoride. Some 357 participants aged 16 to 26 y completed the WAIS-IV, with a mean FSIQ score of 109.2 (95% confidence interval [CI]: 107.8-110.5). The estimates of the multivariable regression models demonstrated slightly higher FSIQ scores among the exposed than the nonexposed. The adjusted β of 100%LEFW versus 0%LEFW was 1.07 (95% CI: -2.86, 5.01) and of having dental fluorosis versus no fluorosis was 0.28 (95% CI: -3.00, 3.57). The hypothesis of noninferiority tests found that FSIQ scores of those exposed and nonexposed to fluoride were equivalent. The study provided consistent evidence that early childhood exposure to fluoride does not have effects on cognitive neurodevelopment.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"243-250"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of Mucosal Integration of Machined versus Anodized Titanium Implants.","authors":"J Dworan, F Aellos, J A Grauer, G Fabbri, K G Harder, S Boccardo, P L Cuevas, I Dawid, M Vicini, J A Helms","doi":"10.1177/00220345241296506","DOIUrl":"10.1177/00220345241296506","url":null,"abstract":"<p><p>The long-term success of dental implants depends on the ability of soft tissues to form a protective barrier, limiting pathogen infiltration into peri-implant tissues. Here, we investigated the impact of an anodized surface modification on mucosal integration. Scanning electron microscopy and surface chemistry characterization were carried out on miniaturized implants. Following placement in fresh extraction sockets of mice, peri-implant tissues were examined at 4 time points. Histology along with quantitative immunohistochemistry for Keratin14, Vimentin, Laminin5, and CD68 were carried out on postimplant day (PID) 3 to assess early events in soft-tissue repair; on PID7, when peri-implant epithelialization was complete; at PID14, when osseointegration was complete; and at PID28, when soft-tissue maturation was nearing completion. In all cases, an intact junctional epithelium served as a reference. These analyses supported 3 conclusions: first, maturation of the peri-implant epithelium (PIE) is a protracted process, consistent with clinical observations. Second, maturation of the soft tissue-implant interface is slower than maturation of the bone-implant interface. Third, there is a benefit, albeit transient, to soft-tissue maturation around an anodized implant surface. Given its prolonged time course, strategies to improve and/or accelerate PIE maturation are likely to have significant clinical benefit.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"270-279"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiancestry Genome-Wide Association Study of Early Childhood Caries.","authors":"P Shrestha, M Graff, Y Gu, Y Wang, C L Avery, J Ginnis, M A Simancas-Pallares, A G Ferreira Zandoná, R N Alotaibi, E Orlova, H S Ahn, K N Nguyen, H M Highland, D Y Lin, J S Preisser, G D Slade, M L Marazita, K E North, K Divaris","doi":"10.1177/00220345241291528","DOIUrl":"10.1177/00220345241291528","url":null,"abstract":"<p><p>Early childhood caries (ECC) is the most common noncommunicable childhood disease-an important health problem with known environmental and social/behavioral influences lacking consensus genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multiancestry population of U.S. preschool-age children (<i>N</i> = 6,103) ages 3 to 5 y participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used International Caries Detection and Assessment System criteria to measure ECC; the primary trait was the number of primary tooth surfaces with caries experience (i.e., dmfs index). We estimated heritability and concordance rates and conducted genome-wide association analyses to estimate overall genetic effects as well as stratified by sex, household water fluoride, and dietary sugar and leveraged combined gene/gene-environment effects using 2-degree-of-freedom joint tests. Common genetic variants explained 24% of ECC phenotypic variance among unrelated individuals, while concordance rates were 0.64 (95% confidence interval [CI] = 0.42-0.79) among monozygotic twins and 0.44 (95% CI = 0.34-0.53) among first-degree relatives. Across all analyses, we identified 21 novel nonoverlapping genome-wide significant loci (<i>P</i> < 5 × 10^-8) and 1 genome-wide significant gene (<i>TAAR6</i>) associated with ECC. The taste receptor activity gene set, with known roles in chemosensing, bacterial recognition, and innate immunity in the oral cavity, was strongly associated with ECC. While no locus remained significant after studywise multiple-testing correction, 3 loci were nominally significant (<i>P</i> < 0.05) and directionally consistent in external cohorts of 285,248 adults (rs1442369, <i>DLGAP1</i> and rs74606067, <i>RP11-856F16.2</i>) and 18,994 children (rs71327750, <i>SLC41A3</i>). Meanwhile, the strongest marker known to be associated with adult caries (rs1122171, tagging the long noncoding RNA <i>PITX1-AS1</i>) was nominally significant (<i>P</i> = 0.01) and directionally consistent with ECC in our study. Taken together, the results of this study add to the genomics knowledge base for early childhood caries, offer several plausible candidates for future mechanistic studies, and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"280-289"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable Hydrogel as Intracanal Medication for Root Canal Disinfection.","authors":"M Cao, D Wu, H Tu, B Mou, J Kang, J Liao, J Yang","doi":"10.1177/00220345241309865","DOIUrl":"https://doi.org/10.1177/00220345241309865","url":null,"abstract":"<p><p>Due to the complex anatomical structures of the root canal, thorough intracanal disinfection has always been challenging in endodontic treatment. Existing intracanal medicaments exhibit limitations such as low permeability and suboptimal antibacterial performance. Thus, an intracanal medicament that combines excellent operating performance with potent antibacterial properties is required. Therefore, we designed an injectable hydrogel loaded with modified triple antibiotic drugs (mTAD) through a Schiff base reaction of carboxymethyl chitosan (CMCS) and polyethylene glycol aldehyde (OHC-PEG-CHO), mTAD/CMCS/OHC-PEG-CHO (mTCP). We subsequently evaluated the characteristics of mTCP. Moreover, the antibacterial capacity of the hydrogels was assessed in vitro. The effects of mTCP on the cell biocompatibility and odonto-/osteogenic differentiation of stem cells from the apical papilla (SCAPs) were also examined. Furthermore, we established a periapical inflammation model in the young permanent teeth of a Beagle dog and explored the effects of mTCP on root canal disinfection and root development. Our findings revealed that mTCP exhibited excellent operability, fluidity, and ease of removal from the root canal. mTCP presented outstanding antibacterial efficacy both in vitro and in vivo, attributed to its exceptional permeability and sustained release of mTAD. The odonto-/osteogenic differentiation of SCAPs was augmented by adding mTCP. Moreover, mTCP facilitated root elongation, dentinal wall thickening, and apical closure in the Beagle dog model. mTCP exhibited a pronounced effect on promoting periapical tissue healing and root development. In conclusion, mTCP hydrogel has promising potential for root canal disinfection in endodontic therapy.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241309865"},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: \"A Deep Learning System to Predict Epithelial Dysplasia in Oral Leukoplakia\".","authors":"J M Aguirre-Urizar, I Lafuente-Ibañez de Mendoza","doi":"10.1177/00220345251317097","DOIUrl":"https://doi.org/10.1177/00220345251317097","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251317097"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to Molecular Profiling of Odontoclasts during Physiological Tooth Replacement.","authors":"","doi":"10.1177/00220345251322122","DOIUrl":"10.1177/00220345251322122","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251322122"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg3 Alleviates Xerostomia in Orchiectomized Mice via AR/AQP5.","authors":"B Chen, Y Sun, W Wei, T Mao, J Yu, Y Cui, Z Lin, L Wang, N Watanabe, K H Mayo, J L Pathak, X Li, J Li","doi":"10.1177/00220345241302321","DOIUrl":"https://doi.org/10.1177/00220345241302321","url":null,"abstract":"<p><p>Sjögren's disease (SjD), an autoimmune inflammatory disease, is associated with reduced androgen levels. Testosterone replacement therapy alleviates SjD progression, but the exact mode of action is unclear and adverse effects are reported. Our present study found that dihydrotestosterone (DHT) enhances the transcription and expression of aquaporin 5 (AQP5) in human salivary gland epithelial cells via androgen receptor (AR) signaling. The DHT/AR complex binds to the androgen response element of the AQP5 promoter, upregulating AQP5 expression. Using orchiectomized mice, we observed that reduced levels of DHT resulted in hyposalivation and SjD progression. By screening compounds with similar structures to DHT, we identified that DHT-like ginsenoside Rg3, a natural product, upregulates AQP5 expression in salivary gland epithelial cells via binding with AR. The Rg3/AR complex acts like DHT/AR and binds to the androgen response element of the AQP5 promoter to promote AQP5 transcription in salivary gland epithelial cells. Gavage of Rg3 restored saliva secretion and submandibular gland morphology in orchiectomized and nonobese diabetic mice. Transcriptome analysis revealed that Rg3 treatment upregulates saliva secretion-related signaling and downregulates inflammation and immune activation-related signaling in the submandibular glands of orchiectomized mice. In conclusion, our results indicated that Rg3 restores androgen deficiency-triggered xerostomia via AR-mediated AQP5 upregulation.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241302321"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Porphyromonas gingivalis</i> Induces Disturbance of Kynurenine Metabolism Through the Gut-Brain Axis: Implications for Alzheimer's Disease.","authors":"H Zhu, C Huang, Z Luo, L Wu, X Cheng, H Wu","doi":"10.1177/00220345241303141","DOIUrl":"https://doi.org/10.1177/00220345241303141","url":null,"abstract":"<p><p><i>Porphyromonas gingivalis</i> is one of the major pathogens of chronic periodontitis. <i>P. gingivalis</i> can cause systemic inflammation, amyloid β protein deposition, and hyperphosphorylation of tau protein, leading to Alzheimer's disease (AD)-like lesions. <i>P. gingivalis</i> oral infection causes gut microbiota alteration, gut barrier dysfunction, and intestinal immune response and inflammation. The microbiota-gut-brain axis has a potential role in the pathogenesis of AD. Whether <i>P. gingivalis</i> affects AD-like lesions via the gut-brain axis needs more study. In this study, orally administered <i>P. gingivalis</i> induced alveolar resorption, intestinal barrier impairment, and AD-like lesions. Oral infection with <i>P. gingivalis</i> induced oral and gut microflora dysbiosis, imbalance of the tryptophan metabolism pathway of gut microbiota, and elevated levels of 3-hydroxykynurenine in the sera and hippocampi. The key metabolite, 3-hydroxykynurenine, suppressed <i>Bcl2</i> gene expression, leading to neuronal apoptosis and promoting AD-like lesions in vivo and in vitro. These findings suggest that <i>P. gingivalis</i> can induce AD pathogenesis through the gut-brain axis, providing new ideas for the prevention and treatment of AD.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241303141"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pericytes Are Odontoblast Progenitor Cells Depending on ER Stress.","authors":"T Ouchi, M Ando, R Kurashima, M Kimura, N Saito, A Iwasaki, H Sekiya, K Nakajima, T Hasegawa, T Mizoguchi, Y Shibukawa","doi":"10.1177/00220345241307944","DOIUrl":"10.1177/00220345241307944","url":null,"abstract":"<p><p>Odontoblasts are terminally differentiated cells that exhibit mechanosensitivity and mineralization capacity. Mechanosensitive ion channels such as Piezo1 are present in odontoblasts and are associated with their physiological functions via Ca²⁺ signaling. Both Ca²⁺ signals via Ca²⁺ influx from mechanosensitive ion channels and Ca²⁺ release from Ca²⁺ stores function as secondary messenger systems for various biological phenomena. The endoplasmic reticulum (ER) serves as an intracellular Ca²⁺ store that mobilizes intracellular Ca²⁺. Changes in Ca²⁺ concentration inside the ER are among the factors that cause ER stress. Perivascular cells are located around odontoblasts in the dental pulp. Although such formation indicates that perivascular cells interact with odontoblasts, their detailed profiles under developmental and pathological conditions remain unclear. In this study, we revealed that pericyte marker, neural/glial antigen 2 (NG2)-positive cells, in cell-rich zones (CZs) can differentiate into Piezo1-positive odontoblasts following genetic odontoblast depletion in mice, and modeled as odontoblast death after severe dentin injury and as reparative dentin formation. NG2-positive pericytes differentiated into odontoblasts faster than glial cells. To determine how NG2-positive cells differentiate into Piezo1-positive odontoblasts, we focused on the ER-stress sensor protein, activating transcription factor 6a (ATF6a). After genetic odontoblast depletion, NG2-positive cells regenerated in the odontoblast layer and were capable of acting as functional odontoblasts. In the presence of extracellular Ca²⁺, the application of a sarco/ER Ca²⁺-ATPase (SERCA) inhibitor, thapsigargin, known as an ER-stress inducer, increased the intracellular Ca²⁺ concentration in the odontoblast lineage cells (OLCs). The increase was significantly inhibited by the application of a pharmacologic Piezo1 inhibitor, indicating that ER stress by SERCA inhibition augmented Piezo1-induced responses in odontoblast progenitor cells. However, the physiological activation of G_q-coupled receptors by adenosine diphosphate did not induce Piezo1 activation. Gene silencing of <i>ATF6a</i> and/or <i>NG2</i> impaired the mineralization of OLCs. Overall, ATF6a orchestrates the differentiation of NG2-positive pericytes into functional odontoblasts that act as sensory receptor cells and dentin-forming cells.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241307944"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}