Journal of dental research最新文献

{"title":"Dental Management of Genetic Dental Disorders: A Critical Review.","authors":"H Dujic, K Bücher, I M Schüler, P Schmidt, S Hertel, J Timpel, A Jablonski-Momeni, R Schilke, I Kapferer-Seebacher, J Zschocke, A Liebermann, J F Güth, D Edelhoff, R Heinrich-Weltzien, J Kühnisch","doi":"10.1177/00220345241305330","DOIUrl":"10.1177/00220345241305330","url":null,"abstract":"<p><p>Genetic dental disorders (GDDs) can occur either isolated or as part of syndromes. Clinically, deviations in tooth shape, size, or structure, as well as the absence of multiple teeth, lead to severe dysfunction and a reduced quality of life, requiring lifelong preventive, conservative, and prosthodontic dental care. The dental management of prevalent dental diseases, such as caries or periodontitis, has been based on decades of research, whereas scientific data on the dental management of GDDs are scarce. This lack of data is challenging for dental practitioners, who must primarily rely on empirical knowledge only. Therefore, a systematic literature search and review were conducted on the dental management of common GDDs, such as ectodermal dysplasia, amelogenesis imperfecta, dentinogenesis imperfecta, periodontitis as a manifestation of rare systemic diseases, and X-linked hypophosphatemia and hypophosphatasia. The review revealed that 468 of the 9,115 retrieved publications met the inclusion criteria, with most being case reports or case series, highlighting a lack of robust clinical trials. This critical review provides a brief summary of the genetic background, key clinical signs, and treatment options for these conditions. The dominance of case reports emphasizes the need for improved reporting standards and long-term follow-up to support comprehensive data synthesis and meta-analyses. In addition, the uneven global distribution of publications suggests disparities in access to advanced dental care for GDDs. Efforts to standardize reporting and improve treatment documentation globally are crucial to addressing these challenges. In this way, information on GDD management can be improved, and statistical analyses of the data can be performed.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"369-379"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191562","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":"The Skin-to-Mucosa Ratio Defines the Osteogenic Potential of Lip Fibroblasts.","authors":"L Parisi, F Mansour, S Rihs, I Schnyder, G C La Scala, C Katsaros, M Degen","doi":"10.1177/00220345251321806","DOIUrl":"https://doi.org/10.1177/00220345251321806","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251321806"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665712","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":"Fighting the Antimicrobial Resistance Global Emergency: The Lifesaving Role of Dentistry.","authors":"W Thompson, F Cieplik, L Teoh, N Jakubovics, H Benzian","doi":"10.1177/00220345251324162","DOIUrl":"10.1177/00220345251324162","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251324162"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665699","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":"Anti-inflammatory Annexin A1 in Periodontitis via Formyl Peptide Receptor 2.","authors":"M Takedachi, M Murata, K Sawada, K Kawasaki, K Kawakami, A Sugimoto, C Morimoto, H Sakashita, Y Usami, C Fujihara, T Iwayama, S Murakami","doi":"10.1177/00220345251322151","DOIUrl":"10.1177/00220345251322151","url":null,"abstract":"<p><p>Although annexin A1 (ANXA1) is known to mediate inflammatory responses through N-formyl peptide receptor 2 (FPR2), the role of the ANXA1-FPR2 signaling pathway in periodontal disease remains unclear. This study investigated the contribution of this pathway to the pathophysiology of periodontal disease. Using a ligature-induced mouse model, we performed histologic analyses to examine ANXA1 and FPR2 expression. We observed upregulation of ANXA1 and FPR2 within the gingiva and periodontal ligament. In vitro analysis of human periodontal ligament cells revealed that interleukin 1β (IL-1β)-induced secretion of IL-8 and granulocyte-macrophage colony-stimulating factor was significantly increased in the presence of WRW4, an FPR2 antagonist. Furthermore, IL-1β-mediated upregulation of IL-8 was significantly enhanced in human periodontal ligament cells by silencing <i>ANXA1</i> and <i>FPR2</i> expression via small interfering RNAs. The effect of the ANXA1-FPR2 signaling pathway on periodontal tissue destruction was also examined in murine periodontitis under daily administration of WRW4 or an ANXA1 N-terminal mimetic peptide, Ac2-26, with micro-computed tomography and histologic analyses. WRW4 administration significantly intensified alveolar bone resorption, increased the number of osteoclasts on the alveolar bone surface, and dilated blood vessels in the periodontal ligament. Conversely, Ac2-26 administration significantly mitigated alveolar bone resorption. Collectively, these findings suggest a role for the ANXA1-FPR2 signaling pathway in attenuating the pathogenesis of periodontal disease by regulating localized inflammatory responses within periodontal tissues.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251322151"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665697","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":"Potential of High-Intensity Focused Ultrasound in Enamel Remineralization.","authors":"B Shrestha, S M Rajan, M Saunders, A Fawzy","doi":"10.1177/00220345251323869","DOIUrl":"10.1177/00220345251323869","url":null,"abstract":"<p><p>Remineralization is an essential interventional strategy for intercepting enamel white spot lesions (WSLs). Given the limitations of both natural and/or fluoride-mediated repair processes, there is a need to develop novel strategies for repairing enamel WSLs via a minimally invasive approach while restoring the unique ultrastructural integrity and functional properties. Inspired by the unique capability of high-intensity focused ultrasound (HIFU) in facilitating the crystallization process, we propose a novel strategy of employing HIFU for in vitro repair of WSLs through synergizing the crystallization process required for hydroxyapatite (HAP) formation from its precursor (calcium phosphate ion clusters; CPICs). Following CPIC formulation and characterization including the resultant amorphous calcium phosphate (ACP), the effect of HIFU on the ACP-to-HAP transition on the amorphous substrate was investigated using transmission electron microscopy and high-resolution transmission electron microscopy, selected area electron diffraction, and X-ray diffraction (XRD). The results showed profound amorphous-to-crystalline phase transition, within 5- to 30-min HIFU exposure, whereas the long axis of the resultant HAP corresponded with the (002) plane, and a lattice spacing of 0.34 nm indicated a preferred <i>c</i>-axis growth direction consistent with the orientation of natural enamel crystallites. For enamel repair, artificial WSLs were created on enamel specimens and then subjected to CPICs, followed by HIFU exposure for 2.5, 5, or 10 min. Scanning electron and atomic force microscopies revealed the decreased surface roughness and the gradual obliteration in the WSL porous structure with continuous linear coaxial arrangement of HAP crystallites filling the prismatic/interprismatic gaps closely resembling sound enamel specifically with 5-min HIFU exposure. Enamel WSL ultrastructural repair was further confirmed from XRD and Raman spectral analyses with the associated regaining of mineral density and nanomechanical properties as reflected from micro-computed tomography (CT) and nanoindentation results, respectively. Micro-CT further validated the subsurface remineralization of WSLs with HIFU exposure. Within the same exposure parameters, HIFU exhibited a potent antibiofilm effect against <i>Streptococcus mutans</i>. This study introduced a new approach for remineralizing enamel WSLs through the potent synergy between HIFU and CPICs.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251323869"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665701","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":"Enhancing Socioeconomic Status Prediction for Cavities: A Hybrid Method.","authors":"A T M Dao, L G Do, N Stormon, H V Nguyen, D H Ha","doi":"10.1177/00220345251324494","DOIUrl":"10.1177/00220345251324494","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251324494"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660142","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":"Effect of <i>L. plantarum</i> on Caries Prevention and the Oral-Gut Microbiome In Vivo.","authors":"Y Wu, N Alomeir, T Li, M L Falsetta, R Yang, Y Liu, E Sun, T T Wu, R Wood, M H Kenney, A Almulhim, G Watson, K-A Torres Ballester, K Fiscella, J Xiao","doi":"10.1177/00220345251325807","DOIUrl":"https://doi.org/10.1177/00220345251325807","url":null,"abstract":"<p><p>While <i>Lactiplantibacillus plantarum</i> has shown promise against cariogenic pathogens, its in vivo effects on caries prevention remain unexplored. This study used a rat model to investigate the effect of <i>L. plantarum</i> early-life oral inoculation on oral and gut microbiomes, host immune responses, and serum metabolites. Forty 14-day Sprague-Dawley rat pups were randomly allocated into 5 groups: (1) blank control, (2) <i>L. plantarum</i> colonization alone, (3) <i>Streptococcus mutans</i> and <i>Candida albicans</i> co-colonization, (4) <i>L. plantarum</i> precolonization before <i>S. mutans</i> and <i>C. albicans</i> exposure, and (5) 2-wk treatment of <i>L. plantarum</i> after <i>S. mutans</i> and <i>C. albicans</i> exposure. Dynamic colonization of <i>L. plantarum</i>, <i>S. mutans</i>, and <i>C. albicans</i> in saliva and plaque was assessed using a culture-dependent method. Saliva, plaque, and fecal microbiomes were assessed using 16S ribosomal RNA gene sequencing. Caries scoring was performed using Keyes' scoring system and microcomputed tomography. Serum metabolite and immune markers were assessed through liquid chromatography tandem mass spectrometry untargeted metabolomics and multiplex immune profiling. We found that 3-d <i>L. plantarum</i> inoculation established stable <i>L. plantarum</i> colonization in the oral cavity of young rats. Inoculation timing of <i>L. plantarum</i> was critical for caries prevention. <i>L. plantarum</i> precolonization significantly reduced caries lesions compared with the <i>S. mutans</i> and <i>C. albicans</i> group, whereas 2 wk of postexposure treatment did not demonstrate a protective effect. <i>L. plantarum</i> precolonization led to distinct microbial shifts in saliva, plaque, and gut microbiomes, with an increased abundance of beneficial bacteria, such as <i>Streptococcus azizii</i>, <i>Bifidobacterium animalis</i>, <i>Faecalibaculum rodentium</i>, and <i>Allobaculum stercoricanis</i>, and a decrease in <i>S. mutans. L. plantarum</i> preinoculation also influenced metabolic profiles, with 1 metabolite upregulated and 24 downregulated, although immune marker differences were minimal. In conclusion, <i>L. plantarum</i> oral colonization before host exposure to oral cariogenic pathogens effectively reduced caries and modulated the profile of oral and gut microbiomes and serum metabolic profile.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251325807"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660140","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":"TREM2 Activation Relieves TMJOA by Stabilizing the Synovial Barrier via Siglec1.","authors":"X Liu, X Luo, M Xiao, J Zhao, W Fang, J Ke, X Long","doi":"10.1177/00220345251320946","DOIUrl":"https://doi.org/10.1177/00220345251320946","url":null,"abstract":"<p><p>Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that plays a vital role in innate immune responses. This study aims to investigate the effect of TREM2 on synovial barrier homeostasis and synovitis during temporomandibular joint osteoarthritis (TMJOA). The expression level of TREM2 is decreased in the synovium of both patients with TMJOA and a mouse model of TMJOA, accompanied by synovial barrier breakdown. TREM2 overexpression inhibits the macrophage inflammatory response ex vivo and relieves synovial inflammation, cartilage degeneration, and synovial barrier destruction in monosodium iodoacetate-induced TMJOA mice. RNA-seq analysis reveals that Siglec1 serves as a downstream signal that is downregulated after TREM2 activation. Further in vivo and in vitro experiments demonstrate that rhSiglec1 treatment promotes the synthesis and release of inflammatory cytokines, such as interleukin-6 and RANTES, in macrophages and reverses the alleviation effect of TREM2 activation on TMJOA synovial barrier disorders, synovial inflammation, cartilage degradation, and bone destruction. Overall, this study verifies that TREM2 activation alleviates TMJOA pathology by maintaining synovial barrier homeostasis and inhibiting synovial inflammation. These findings provide new insight into the mechanism of TREM2 in the pathogenesis of TMJOA.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251320946"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660152","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":"ZDHHC9-Mediated PKG1 Affects Osteogenesis by Regulating MAMs in T2DM.","authors":"B Y Li, G Q Ma, H D Gui, S J Zhou, Y X Liu, A L Wu, Q X He, J Y Chen, J Y Diao, D N Wu, X Xu, D J Zhang","doi":"10.1177/00220345251321776","DOIUrl":"https://doi.org/10.1177/00220345251321776","url":null,"abstract":"<p><p>Palmitoylation is recognized as a prevalent posttranslational modification of proteins, which is highlighted in recent studies as a key player in regulating protein stability, subcellular localization, membrane transport, and other cellular biological processes. However, its role in peri-implant osteogenesis under type 2 diabetes mellitus (T2DM) remains unclear. During this study, the in vitro high-glucose model based on MC3T3-E1 cells demonstrated that a high-glucose environment in vitro markedly inhibited osteoblasts proliferation and osteogenesis; meanwhile, ZDHHC9 emerged as a significantly upregulated protein. Then, <i>Zdhhc9</i> knockdown improved the dysfunction of osteoblasts and peri-implant osteogenesis of T2DM mice. In addition, co-immunoprecipitation and fluorescence co-localization analysis revealed an interaction between ZDHHC9 and cyclic guanosine monophosphate (GMP)-dependent protein kinase G 1 (PKG1), and silencing of <i>Prkg1</i> prevented the improvement in osteoblasts with <i>Zdhhc9</i> knockdown. Furthermore, we verified that <i>Zdhhc9</i> knockdown and <i>Prkg1</i> silencing altered the distance between the endoplasmic reticulum and mitochondria and the expression of mitochondria-associated endoplasmic reticulum membranes (MAMs)-related proteins in osteoblasts. Collectively, our data show that ZDHHC9 could regulate MAMs through palmitoylation of PKG1 to induce osteoblast dysfunction in T2DM. ZDHHC9 might become a novel therapeutic target for peri-implant osteogenesis in diabetes patients.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251321776"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660157","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":"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}