Journal of Dental Research最新文献

{"title":"Comparative Diagnostic Performance of Oral Microbial Habitats for Periodontitis","authors":"I. Tomás, B. Suárez-Rodríguez, T. Blanco-Pintos, A. Sánchez-Barco, M. Alonso-Sampedro, M.J. Carreira, A. Regueira-Iglesias, C. Balsa-Castro","doi":"10.1177/00220345261473819","DOIUrl":"https://doi.org/10.1177/00220345261473819","url":null,"abstract":"Periodontitis affects more than 1 billion people worldwide but remains largely underdiagnosed. The oral microbiota offers a noninvasive diagnostic window, but studies based on 16S rRNA data have reported heterogeneous and often suboptimal performance. It remains unclear which oral habitat and modeling strategy best support clinical decision making. We analyzed 2,303 adult samples from 33 publicly available 16S rRNA V3-V4 Illumina projects encompassing saliva, supragingival, and subgingival habitats. Amplicon sequence variants (ASVs) were identified against the expanded Human Oral Microbiome Database. Compact microbial signatures were identified through multivariate techniques (sparse partial least squares discriminant analysis and a customized genetic algorithm). Five machine-learning algorithms were benchmarked under repeated cross-validation and test-set evaluation. Diagnostic performance was assessed using the area under the receiver-operating characteristic curve (AUC), and clinical net benefit was assessed using decision curve analysis (DCA). Generalized additive models (GAMs) provided the best discrimination with compact panels of 6 to 12 ASVs. Saliva and supragingival achieved the best discrimination (AUC = 0.928 and 0.903; sensitivity = 92.4% and 87.6%; specificity = 85.3% and 81.7%), significantly outperforming subgingival plaque (0.803, 78.2% and 75.1%, respectively; adjusted <jats:italic toggle=\"yes\">P</jats:italic> ≤ 0.001). DCA further demonstrated the highest and most stable net clinical benefit in saliva (AUC-DCA = 0.437), followed by supragingival (0.419) and subgingival (0.331). Forty-eight taxonomically annotated ASVs emerged as predictors, underscoring the models’ biological interpretability. In subgingival sites, the most prevalent features were health-associated commensals, such as <jats:italic toggle=\"yes\">Streptococcus oralis</jats:italic> subsp. <jats:italic toggle=\"yes\">dentisani</jats:italic> . Supragingival plaque and saliva predominantly revealed periodontitis-associated taxa, including <jats:italic toggle=\"yes\">Porphyromonas gingivalis</jats:italic> and <jats:italic toggle=\"yes\">Filifactor alocis</jats:italic> . Thus, saliva and supragingival plaque better capture the microbial fingerprint of periodontitis-associated dysbiosis. Oral microbiome–based models across habitats showed consistent diagnostic performance for periodontitis. The GAM algorithm with compact, interpretable microbial signatures achieved strong discrimination and superior net benefit in saliva and supragingival samples, highlighting its potential for translation into scalable, noninvasive diagnostic tools for precision periodontics.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"9 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Health Mediates Income Decline Over Time in Australian Adults","authors":"A.C. Kalhan, R. Blythe, T.A. Kalhan, K.G. Peres, M.A. Peres","doi":"10.1177/00220345261471419","DOIUrl":"https://doi.org/10.1177/00220345261471419","url":null,"abstract":"The objective of this study was to investigate if poor oral health mediates income losses over a 12-y follow-up period in Australian adults. Data were obtained from adults aged ≤65 y, selected to minimize the influence of retirement, who participated in both waves (2004–2006 and 2017–2018) of the National Study of Adult Oral Health (NSAOH), nationally representative surveys of Australians aged ≥15 y. Baseline household income, categorized as low ($80,000), was the exposure, and follow-up household income was the outcome, which was inflation-adjusted using the Consumer Price Index (CPI) to ensure comparability across both waves and account for changes in purchasing power over time. Change in self-reported oral health, categorized as “good” (excellent/very good/good at both waves) or “poor” (persistently poor or declined to poor), was examined as a mediator. Marginal structural models using multinomial logistic regression and inverse probability weighting estimated indirect (mediated) effects of poor oral health on income loss, adjusting for sociodemographic and behavioral confounders. Missing data were handled using multiple imputation, and E-values assessed robustness to unmeasured confounding. A total of 707 adults were included (mean [SD] age at baseline: 41.4 [8.17] y; males: 40.6%). At baseline, 19.6%, 46.7%, and 33.7% reported low, medium, and high income, respectively, and 15% reported poor oral health. Compared to high baseline income, individuals with medium income had a 3.10 times higher risk of shifting to low income (vs. high income) at follow-up, with poor oral health mediating 5% to 7% of this effect. The population-attributable fraction for the mediated effect was 2.1%, equivalent to approximately 376,932 Australian adults whose income decline may be partly explained by deteriorating oral health. Poor oral health partially mediated long-term income decline among Australian adults, underscoring the sustained economic burden of oral health inequalities.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"59 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Determination of the Frontonasal Identity of Neural Crest Cells","authors":"N. Adhikari, P.P.R. Iyyanar, Z. Wu, C. Qin, C. Ahn, Y.-C. Hu, H.W. Lim, Y. Lan, R. Jiang","doi":"10.1177/00220345261471833","DOIUrl":"https://doi.org/10.1177/00220345261471833","url":null,"abstract":"The entire vertebrate facial skeleton is derived from Hox-negative cranial neural crest cells (CNCCs) that populate the embryonic frontonasal prominence and the first pharyngeal arches. Previous studies have shown that the Edn1/Ednra-Dlx5/Dlx6-Hand2 regulatory network specifies the maxillomandibular identity of CNCCs in the first pharyngeal arches in mice and that the combined application of retinoic acid and noggin to the presumptive maxillary domain in avian embryos transformed maxillary tissues to frontonasal structures, but the molecular mechanisms regulating frontonasal CNCC identity remain unresolved. Biallelic loss of function of any of the <jats:italic toggle=\"yes\">aristaless-like</jats:italic> homeobox genes, including <jats:italic toggle=\"yes\">ALX1</jats:italic> , <jats:italic toggle=\"yes\">ALX3</jats:italic> , and <jats:italic toggle=\"yes\">ALX4</jats:italic> , which exhibit partly overlapping patterns of expression in the frontonasal CNCCs, causes frontonasal dysplasia. In this study, we show that mice with combined inactivation of <jats:italic toggle=\"yes\">Alx1</jats:italic> and <jats:italic toggle=\"yes\">Alx3</jats:italic> throughout CNCCs exhibit disruption of frontonasal CNCC identity with ectopic activation of maxillary CNCC developmental profiles. We show that transgenic <jats:italic toggle=\"yes\">Alx1</jats:italic> expression throughout the CNCCs, starting from when they were migrating toward the facial primordia, caused ectopic activation of frontonasal CNCC marker genes and suppression of the maxillomandibular marker genes in the developing maxillary and mandibular processes and resulted in the formation of duplicated premaxilla at the expense of maxillary structures. These data identify the ALX transcription factors as key regulators specifying frontonasal CNCC identity and fill a long-standing gap in the molecular mechanism patterning the regional identities of the CNCC-derived craniofacial mesenchyme.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"26 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148858752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal Enamel Mineralization and Hypercalcemia due to GNA11 Variants","authors":"N. Obtel, A. Le Cabec, A.-L. Lakhel, A. Attia, C. Andrique, F. Hermans, F. Kovaci, T.N. Nguyen, A. Chansavang, A. Percot, C. Torrens, D. Vangu, F. Vaysse, M. Gadion, F. Savagner, T. Edouard, A. Bloch-Zupan, B. Lukić, A. Rack, A. Brunelle, A. Linglart, E. Pasmant, F. Ramirez Rozzi, F.M. Hannan, C. Gaucher, T. Coradin, R.V. Thakker, J.-P. Bertocchio, C. Chaussain","doi":"10.1177/00220345261470370","DOIUrl":"https://doi.org/10.1177/00220345261470370","url":null,"abstract":"Abnormal enamel mineralization has been reported in genetic conditions associated with hypocalcemia but never with hypercalcemia. In the present study, we report 10 patients from 2 unrelated families in whom hypomineralized enamel co-segregated with hypercalcemia due to a complete deletion or frameshifting premature truncation (p.(Ser18Argfs*2)) of the guanine nucleotide–binding protein (G-protein) subunit α <jats:sub>11</jats:sub> ( <jats:italic toggle=\"yes\">GNA11</jats:italic> ) gene. Both <jats:italic toggle=\"yes\">GNA11</jats:italic> variants were heterozygous and predicted to cause a loss of function of Gα <jats:sub>11</jats:sub> . Multiproxy imaging analyses of naturally exfoliated primary teeth and clinically extracted permanent teeth from 2 affected patients revealed abnormal enamel mineralization, with constitutive patches of hypomineralization following no set pattern. In parallel, the study of wild-type mouse tooth germs using combined molecular and protein analyses showed <jats:italic toggle=\"yes\">Gna11</jats:italic> and Gα <jats:sub>11</jats:sub> protein expression in ameloblasts at the secretion and maturation stages, as well as in odontoblasts, suggesting a role for Gα <jats:sub>11</jats:sub> in tooth formation. Furthermore, the analysis of a mouse model of Familial Hypocalciuric Hypercalcemia 2 (FHH2) revealed delayed onset of enamel mineralization in the continuously growing incisors and hypomineralized enamel in both incisor and molars of heterozygous ( <jats:italic toggle=\"yes\">Gna11</jats:italic> Tm1b <jats:sup>+/−</jats:sup> ) mice, with defects that are very similar to those affecting human FHH2 teeth. In conclusion, our study reveals that abnormal enamel mineralization may occur in association with hypercalcemia due to loss-of-function <jats:italic toggle=\"yes\">GNA11</jats:italic> mutations, opening a new field of investigation and highlighting the need to include a dentist in the multidisciplinary team in charge of patients with monogenic calcium disorders.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"280 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148858741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Fibrin Deposit Alleviates Periodontitis via Neutrophil Modulation","authors":"B. Zhang, J. Wang, T. Wang, Z. Zong, X. Liu, Z. Xu, H. Zhang, Y. Wang, J. Feng, D. Wang, S. Wang, Y. Zhang, X. Yang, W. Zhao, J. Li, S. Ge","doi":"10.1177/00220345261468280","DOIUrl":"https://doi.org/10.1177/00220345261468280","url":null,"abstract":"Periodontitis is a chronic inflammatory disease characterized by dysregulated neutrophil responses that contribute to progressive periodontal tissue destruction. Here, we observed aberrant fibrin accumulation in inflamed periodontal tissues and hypothesized that fibrin acts as a pathogenic mediator that promotes neutrophil recruitment and activation, thereby triggering neutrophil extracellular traps (NETs) formation and reactive oxygen species (ROS) production. To therapeutically target fibrin deposition, we developed a ROS-responsive hydrogel (PVHA@tPA) that enables localized delivery of tissue plasminogen activator (tPA), activating plasminogen to mediate fibrin degradation. In vitro, tPA released from the hydrogel degraded fibrin matrices in the presence of plasminogen, which restrained fibrin-mediated neutrophil adhesion and migration while suppressing subsequent NETs formation and ROS overproduction. By attenuating this neutrophil overactivation, the treatment improved the osteogenic capacity of periodontal ligament stem cells (PDLSCs) and the angiogenic potential of human umbilical vein endothelial cells (HUVECs). In vivo, PVHA@tPA treatment in a mouse periodontitis model reduced gingival fibrin deposition, attenuated neutrophil-associated inflammation, downregulated proinflammatory factors, and alleviated alveolar bone loss. Together, these findings identify fibrin deposition as a key driver of neutrophil dysregulation in periodontitis and establish fibrin-targeted therapy as a promising strategy to rebalance neutrophil responses and ameliorate periodontitis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"17 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148858758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Plot Twist in the Tale of Dental Cubic Zirconia—and a (Dis)course Correction","authors":"R. Belli, U. Lohbauer","doi":"10.1177/00220345261471408","DOIUrl":"https://doi.org/10.1177/00220345261471408","url":null,"abstract":"Different scientific fields occasionally have to deal with the problem of imprecision when definitions cross disciplinary boundaries and extend beyond the scope of technical oversight. This occurred when dentistry adopted ambiguous phase descriptions for zirconia materials from a ceramics community that was still grappling with methodological uncertainties. Here, we recount the origins of dental zirconia being mistakenly referred to as “cubic” as well as the reasons underlying the difficulties in accurately assessing crystallographic phase structures in such materials. We highlight compelling new evidence that corroborates earlier studies suggesting that zirconia within the compositional range of stabilization used in dentistry is fully tetragonal upon cooling from the sintering temperature.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"85 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages Promote Vascular Maturation to Support Tooth Germ Morphogenesis","authors":"Z. Wang, M. Wang, R. Zhang, J. Wang, Y. Zhang, J. Wang, L. Wang, J. Liu, D. Zhao, Z. Zhang, S. Wang, F. Wei","doi":"10.1177/00220345261470395","DOIUrl":"https://doi.org/10.1177/00220345261470395","url":null,"abstract":"Macrophages are increasingly recognized as key regulators of organogenesis, yet their contributions to tooth germ development remain poorly understood. Here, we integrated analysis of publicly available single-cell RNA sequencing datasets with multiplex immunohistochemistry to investigate the presence, distribution, and activation states of macrophages during tooth development. Macrophages were enriched in the dental follicle and dental papilla, expanded through local proliferation, and displayed a predominant tissue-resident macrophage (TRM)–like and M2-like phenotype. Spatial and transcriptomic analyses further revealed that macrophages preferentially localized adjacent to developing blood vessels and established a localized provascular niche enriched for vascular regulatory signaling pathways. Functional depletion of macrophages, both in vivo using <jats:italic toggle=\"yes\">Cx3cr1</jats:italic> -dependent DTA mice and ex vivo with clodronate liposomes, impaired tooth germ growth and morphogenetic progression, accompanied by reduced tooth germ size, abnormal cusp morphology, increased apoptosis, and impaired vascular maturation. Notably, macrophage depletion reduced vascular maturation without markedly affecting overall vascular density. Given the well-established requirement for vascular maturation in tooth development and the close spatial association between macrophages and developing vessels, we examined whether macrophages contribute to the immune-vascular interactions required for morphogenesis. Macrophages expressed multiple vascular regulatory factors, including VEGFA, TGF-β, and IL1B, while inhibition of vascular maturation phenocopied the developmental abnormalities caused by macrophage depletion and was associated with attenuated bone morphogenetic protein–associated signaling. Together, these findings identify macrophages as important upstream regulators of tooth germ morphogenesis, acting in part by modulating vascular maturation, and provide new insights into immune-vascular crosstalk during tooth development.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"38 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Independent Roles of Host and Bacterial PAD Enzymes in Periodontitis","authors":"X. Su, H.J. Busscher, H. Dang, M. Yang, X. Jiang, Q. Zhang, K. Tuerhong, X. Luo, H. Wang, M. Wang, Y. Li, S. Yang","doi":"10.1177/00220345261469554","DOIUrl":"https://doi.org/10.1177/00220345261469554","url":null,"abstract":"Periodontitis is a chronic inflammatory disease that frequently continues to progress despite therapy, indicating that pathogenic mechanisms remain insufficiently understood. Citrullination, a posttranslational modification implicated in autoimmune diseases, has emerged as a potential contributor to chronic periodontal inflammation. In periodontitis, citrullination can be mediated by at least 3 distinct enzymes: host-derived peptidylarginine deiminase 2 (PAD2) and peptidylarginine deiminase 4 (PAD4) and bacteria-derived <jats:italic toggle=\"yes\">Porphyromonas gingivalis</jats:italic> peptidylarginine deiminase (PPAD) secreted by the keystone pathogen <jats:italic toggle=\"yes\">P gingivalis</jats:italic> . However, their relative stage- and progression-grade-dependent contributions to human periodontitis remain unclear. In this cross-sectional clinical study, 70 subjects were classified as possessing a healthy periodontium or showing symptoms of gingivitis or different periodontitis stages (stages I–IV). Periodontitis was additionally stratified by its progression grade (grades A–C). Gingival crevicular fluid (GCF) and periodontal tissues were collected. PAD2, PAD4, and PPAD levels in GCF were quantified by enzyme-linked immunosorbent assay, and periodontal tissues were examined by histology and immunofluorescence for citrullinated proteins, PAD2, PAD4, and PPAD. Citrullinated proteins were markedly increased in periodontal tissues from periodontitis patients. PAD2 and PAD4 expression levels were locally elevated within tissues. Opposite to PAD2 levels, PAD4 levels in GCF peaked in gingivitis and tended to decline with periodontitis stage, showing no association with progression grade. PAD2 expression increased with progression grade only when heavy smokers were excluded from the analysis. PPAD expression was increased in gingivitis, further increasing toward stage II periodontitis, after which PPAD expression leveled off. Increasing PPAD levels were strongly associated with the progression grade of periodontitis. Host PAD2 and PAD4 levels in GCF were not correlated and neither were host PADs and bacterial PPAD levels. These findings demonstrate that different host-derived PADs and bacteria-derived PPAD display distinct and independent expression dynamics across disease stages, with PPAD uniquely linked to progressive periodontal destruction. This differential regulation identifies citrullination as a stage-specific mechanism in periodontitis and highlights bacterial PPAD as a potential driver of disease progression.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"4 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dental Pulp Stem Cells Transfer Mitochondria via Tunneling Nanotubes to Drive Hypoxic Angiogenesis","authors":"S. Yang, J. Liu, D.S. Thalakiriyawa, J. Liu, X. Yang, C.K.Y. Yiu, W.L. Dissanayaka","doi":"10.1177/00220345261473588","DOIUrl":"https://doi.org/10.1177/00220345261473588","url":null,"abstract":"The dental pulp resides within a rigid dentin chamber with a limited blood supply, creating a hypoxic environment that impedes tissue regeneration. While growth factor signaling in pulpal revascularization is well documented, the direct cellular mechanisms that protect endothelial cells (ECs) from hypoxia-induced apoptosis remain unclear. This study identifies intercellular mitochondrial transfer (MT) from dental pulp stem cells (DPSCs) to ECs as a critical survival and angiogenic mechanism under hypoxic stress. Using MitoTracker labeling and flow cytometry, we demonstrated that mitochondria are preferentially transferred from DPSCs to ECs, a process significantly upregulated by hypoxia. We found that contact-dependent mechanisms involving tunneling nanotube–like structures contribute to MT, as cytochalasin B treatment or Miro1 knockdown in DPSCs significantly reduced MT and impaired EC function. To assess the impact of this organelle exchange, we isolated mitochondria-recipient (Mito+) and nonrecipient (Mito–) ECs for analysis. Mito+ ECs exhibited enhanced mitochondrial membrane potential, improved energy metabolism, and yielded superior tube-forming capacity as compared with Mito– ECs. Furthermore, MT significantly reduced EC apoptosis under cobalt chloride–induced hypoxic stress. The in vivo Matrigel plug assay showed that inhibiting MT from DPSCs, genetically or by inhibiting mitochondrial respiration, markedly suppressed DPSC-supported angiogenesis and increased EC apoptosis. Mechanistically, RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that MT revives the EC transcriptome and activates the PI3K-AKT signaling pathway. Immunofluorescence confirmed upregulation of AKT signaling in recipient ECs and colocalization of P-AKT with transferred mitochondria. Furthermore, inhibition of AKT signaling with MK-2206 abolished the proangiogenic and prosurvival role associated with MT, suggesting a direct regulatory role. Collectively, these findings establish MT as a vital metabolic lifeline that prevents EC collapse and drives DPSC-supported angiogenesis in the hypoxic pulp during the vulnerable window of pulpal restoration, thereby emphasizing MT as a transformative regenerative endodontic target.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"160 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained Release of eDNA-Degrading Enzymes for Antibiofilm Dental Resins","authors":"T. Wu, H. Kitagawa, N.S. Jakubovics, R. Kitagawa, K. Tsuiki, A.M. Wayes, M.R. Elbadawey, J.G. Burgess, J. Powell, M.J. German, S. Imazato","doi":"10.1177/00220345261466562","DOIUrl":"https://doi.org/10.1177/00220345261466562","url":null,"abstract":"The persistence of oral biofilms on teeth and dental restorative/reconstructive materials is promoted by their extracellular matrix (ECM), which stabilizes microbial communities and restricts antimicrobial penetration. Extracellular DNA (eDNA) is a conserved structural component of the ECM produced by multiple oral microorganisms and represents a promising target for biofilm control. NucB, a nonsequence-specific extracellular endonuclease, degrades eDNA and disperses diverse biofilms without direct bactericidal activity. In this study, we developed a sustained-release system for NucB using nonbiodegradable particles composed of 2-hydroxyethyl methacrylate and trimethylolpropane trimethacrylate (TMPT), and we evaluated the antibiofilm effects of NucB-loaded particles and dental resins incorporating these particles. NucB-loaded poly(2-hydroxyethyl methacrylate)/TMPT (polyHEMA/TMPT) particles released active enzyme for up to 28 d, with an initial burst followed by diffusion-controlled release. The released NucB retained DNA-digesting activity and significantly reduced <jats:italic toggle=\"yes\">Streptococcu mutans</jats:italic> biofilm biomass and structural integrity without affecting bacterial growth or membrane integrity, consistent with ECM-targeted activity. Polymethyl methacrylate (PMMA) resins containing ≥10 wt% NucB-loaded polyHEMA/TMPT particles showed sustained NucB release for 28 d and inhibited <jats:italic toggle=\"yes\">S. mutans</jats:italic> biofilm formation while maintaining flexural strength and modulus at loadings up to 30 wt%. Time-course analyses showed that NucB reduced eDNA accumulation from the earliest stages of biofilm development, thereby preventing dense microcolony assembly and maintaining sparse, discontinuous structures for at least 48 h. In a saliva-derived multispecies model, the PMMA resin containing 10 wt% NucB-loaded polyHEMA/TMPT particles significantly reduced biofilm biomass while preserving bacterial membrane integrity, demonstrating matrix-level activity in complex communities. In this study, we established a nonbiodegradable delivery system that enables sustained NucB release and persistent ECM disruption without compromising the mechanical properties of dental resins. This approach provides a promising strategy for developing biofilm-resistant dental materials to improve control of clinically relevant oral biofilms.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"15 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}