Journal of dental research最新文献

{"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":"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":"439-448"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","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":"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":"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":"428-438"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","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":"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":"Mechanisms Tackling Salivary Gland Diseases with Extracellular Vesicle Therapies.","authors":"P Sawutdeechaikul, S Hwang, J Klangprapan, T V Phan, C Buu Lam, Y-J Yoon, S Seo, S Hong, J-Y Lim, J N Ferreira","doi":"10.1177/00220345251319295","DOIUrl":"https://doi.org/10.1177/00220345251319295","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are lipid-enclosed particles released from cells, containing lipids, DNA, RNA, metabolites, and cytosolic and cell surface proteins. EVs support intercellular communication and orchestrate organogenesis by transferring bioactive molecules in between cells. Mesenchymal stem cells are known to produce EVs, which exhibit immunomodulatory and regenerative capabilities in many target organs, including the salivary glands (SGs). Since cell-based therapies still pose challenges (e.g., donor variability, limited hemocompatibility, and safety), specific EVs may constitute a therapeutic alternative for SG diseases. New EV guidelines (MISEV2023) have recently been updated and reported by our consortium to consolidate the principles of EV biology and expand the boundaries toward innovative therapies. These guidelines provide valuable guidance for researchers to consistently assess the effectiveness of mesenchymal stem cell-derived EV cargo cues, such as microRNA, proteins, and other molecules, to target SG diseases. This review provides a narrative synthesis of preclinical studies on EVs by highlighting EV mechanisms and their potential therapeutic applications for SG diseases, such as radiotherapy-induced SG hypofunction and Sjögren's syndrome, as well as inflammatory and aging-related SG conditions. Additionally, we highlight key areas of the MISEV2023 guidelines that will support future EV-based therapies in SG research. This review adhered to PRESS guidelines (Peer Review of Electronic Search Strategies) and utilized established databases, including Medline/PubMed, Embase, Web of Science, and Scopus, alongside machine learning tools for sorting the most impactful EV studies for SG diseases.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251319295"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712479","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":"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":"https://doi.org/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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665699","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":"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":"https://doi.org/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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665701","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":"Factors Involved in Enamel Knot Establishment and Cap Formation.","authors":"K Steklikova, L Dalecka, J Kubovciak, C Corneloup, S Pantalacci, M Hovorakova","doi":"10.1177/00220345251316834","DOIUrl":"https://doi.org/10.1177/00220345251316834","url":null,"abstract":"<p><p>Development of dentition is a commonly studied process as a representative of the development of ectodermal derivates. A key step is the formation of a signaling center called the enamel knot (EK), which organizes tooth crown formation. In the mouse lower jaw, the anterior part of the tooth-forming region undergoes a series of complex events before the first molar primary EK can form more posteriorly and the tooth can progress through the cap stage. Although much is known about the molecular factors involved in tooth development, disentangling their specific roles is difficult. In this study, we circumvented this problem by isolating the posterior part of the tooth-forming region at embryonic day 13.5 and cultivating it in vitro. By treating them with molecules activating or inhibiting Sonic hedgehog (Shh) and fibroblast growth factor (Fgf) pathways, we demonstrate that Shh plays the role of an inhibitor of EK formation, and we suggest that the FGF pathways may have both positive and negative roles, as seen in hair. By RNA-sequencing of the cultivated isolates after 0, 16, or 24 h in vitro, respectively, we screened for genes whose expression varies with EK and cap formation and pointed to <i>Cdkn2b</i> and <i>Sema3b</i> as 2 promising candidates in this process.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251316834"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660144","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":"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":"https://doi.org/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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660142","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}