Journal of Dental Research最新文献

{"title":"CD69 Regulates Gingival Inflammation and Microbiome in Periodontitis","authors":"F.M. Saavedra, L. Fischer, P.D. Bittner-Eddy, K.F. Johnstone, J.M. Stolley, D.W. Williams, M.C. Herzberg, M. Costalonga","doi":"10.1177/00220345251383827","DOIUrl":"https://doi.org/10.1177/00220345251383827","url":null,"abstract":"Dysbiotic subgingival biofilms initiate periodontitis, while the consequential destruction of periodontal tissues results from a dysregulated local immune response. Interstitial CD4 <jats:sup>+</jats:sup> T cells play a crucial role in orchestrating periodontal inflammation. Upon activation, CD4 <jats:sup>+</jats:sup> T cells express CD69 receptors, which can influence their migration patterns, phenotype, and function during inflammation. Here, we report that in the absence of CD69, memory CD4 <jats:sup>+</jats:sup> T cells (mCD4 <jats:sup>+</jats:sup> T cells) derived from gingival and cervical lymph nodes (cLNs) display an increased proinflammatory phenotype. Following in vitro activation, negative-selected mCD4 <jats:sup>+</jats:sup> T cells from cLNs of CD69 <jats:sup>KO</jats:sup> mice showed enhanced expression of interleukin (IL)–17A ( <jats:italic toggle=\"yes\">P</jats:italic> = 0.0043) and interferon-γ ( <jats:italic toggle=\"yes\">P</jats:italic> = 0.0479). Although comparable to untreated wild-type (WT) mice in the absence of disease, CD69-deficient mice showed augmented alveolar bone loss and a greater interstitial inflammatory cell infiltrate after 7 d of ligature-induced experimental periodontitis. Furthermore, gingival CD4 <jats:sup>+</jats:sup> T cells derived from mice lacking CD69 produced significantly higher levels of IL-17A compared with WT animals. 16S rRNA gene sequencing and bioinformatics analyses of the subgingival microbiota associated with ligatures indicated that the absence of CD69 in the host significantly shaped the composition of the periodontitis-associated biofilm. Therefore, our data suggest that CD69 receptors play a regulatory role in both the cellular and microbial microenvironments associated with periodontitis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"35 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609841","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":"Addressing Selection and Confounding Biases in Dental Claims Data: A Causal Inference Framework for Periodontal–Systemic Disease Research","authors":"J.J. Wong, O. Urquhart, A. Carrasco-Labra, E.F. Schisterman, M. Glick","doi":"10.1177/00220345251387660","DOIUrl":"https://doi.org/10.1177/00220345251387660","url":null,"abstract":"Administrative health care data offer unique opportunities to investigate relationships between oral and systemic diseases. However, these data sources introduce methodological challenges that can compromise causal inference. This article demonstrates how, in the context of claims databases, selection bias (i.e., arising from restricting analyses to individuals with both dental and medical insurance) creates a collider structure that can distort estimates of periodontal treatment effects on systemic disease outcomes. Drawing on causal inference theory, we distinguish between confounding (resulting from common causes) and selection bias (resulting from common effects) and demonstrate how directed acyclic graphs (DAGs) can identify these biases and inform rigorous analytical strategies. Therefore, the goal of this article is to demonstrate how selection and confounding biases in administrative health care claims data can compromise causal inference in periodontal–systemic disease research and to introduce methodological approaches for addressing these threats. Our review of 7 studies investigating periodontal–systemic disease associations using claims data reveals methodological gaps in addressing selection bias in the current literature. Moreover, through a numerical example, we illustrate how selection bias can not only distort but also potentially reverse observed associations, producing contradictory clinical recommendations. To address these methodological threats, we introduce established causal inference strategies, referencing implementation tutorials: for confounding, we reference G-methods (G-formula, inverse probability weighting) and stratification-based approaches (regression, matching); for selection bias, we reference inverse probability of selection weighting approaches when data on nonselected individuals are available. To improve methodological rigor in oral–systemic research, we advocate for (1) routine use of DAGs with freely available software, (2) application of bias-correction techniques using established statistical packages, and (3) transparent reporting of bias assessment procedures. Strengthening causal inference methodology in dental research is paramount to building a robust evidence base on periodontal–systemic relationships that supports clinical decision making and integration of oral health into broader health care frameworks.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"27 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599757","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":"Understanding the Periodontitis–Diabetes Linkage: Mechanisms and Evidence","authors":"D.T. Graves, M.A. Levine, S. Aldosary, R.T. Demmer","doi":"10.1177/00220345251388340","DOIUrl":"https://doi.org/10.1177/00220345251388340","url":null,"abstract":"Diabetes mellitus (DM) and periodontitis share a complex, bidirectional relationship, with each condition exacerbating the other. Diabetes, particularly when poorly controlled, significantly increases the risk, severity, and progression of periodontitis. The biological mechanisms involved are complex and numerous. Hyperglycemia in diabetes is linked to oral microbial dysbiosis, which is in turn associated with increased inflammation, epithelial barrier dysfunction, impaired neutrophil and macrophage function, altered T-cell profiles, and cytokine imbalance, collectively fostering chronic inflammation and immune dysregulation. Moreover, diabetes alters bone metabolism, promoting osteoclastogenesis and reducing reparative bone regeneration by limiting coupled bone formation through an effect on growth factor production, mesenchymal stems cells, and osteoblasts. Conversely, periodontitis is strongly linked to poor glycemic control. Clinical studies and longitudinal meta-analyses report consistent positive associations, while randomized controlled trials show that periodontal therapy reduces HbA1c by ~0.43%. Emerging evidence suggests that periodontitis and oral preclinical dysbiosis contribute to diabetogenesis, although causality remains uncertain. Periodontitis may drive metabolic dysfunction through several biological mechanisms. The dysbiotic oral microbiome and subsequent periodontitis may promote systemic inflammation and subsequent insulin resistance and glucose intolerance. Moreover, oral dysbiosis may deplete nitrate-reducing taxa and impair nitric oxide pathways, which has relevance to both periodontal and cardiometabolic health. Accordingly, periodontal treatment in diabetic populations has shown potential health care savings. Nevertheless, trials assessing the influence of periodontitis treatment on systemic outcomes consistently show significant treatment heterogeneity, which requires explication in future studies. This review underscores the systemic implications of periodontitis in diabetes and highlights the value of integrating periodontal care into diabetes management. A better understanding of the shared pathophysiology between these diseases supports interdisciplinary approaches and points toward novel preventive and therapeutic strategies targeting inflammation, microbial balance, and host response modulation to jointly benefit periodontal and cardiometabolic health.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"3 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599756","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":"LinkMD: Linking Medical and Dental Records with 4 Linking Algorithms.","authors":"J S Patel,E Dinh","doi":"10.1177/00220345251383863","DOIUrl":"https://doi.org/10.1177/00220345251383863","url":null,"abstract":"Despite well-established connections between oral and systemic health, electronic health records (EHRs) and electronic dental records (EDRs) remain largely siloed due to infrastructural and interoperability challenges. This separation limits interdisciplinary care and data-driven research to generate practice-based evidence. We developed and validated 4 algorithmic frameworks specifically designed to link EHR with EDR across nonintegrated systems. Using data from more than 1.7 million medical records and 222,480 dental records spanning a 10-y period at Temple University, we evaluated 4 linkage strategies: (1) direct Social Security number matching, (2) unweighted similarity scoring, (3) weighted average similarity scoring, and (4) a probabilistic expectation-conditional maximization classification model. We compared these approaches using expert-reviewed validation of 1,000 candidate record pairs and selected optimal similarity thresholds for high-fidelity linkages. Our weighted average similarity algorithm demonstrated the best performance with 100% specificity (correctly avoiding false matches), 99% sensitivity (correctly identifying all true matches), and 99% accuracy (proportion of all correct linkages out of total comparisons) at the threshold of 0.82 for successfully linking 121,771 unique patients and 144,229 patients' linkage with 96% sensitivity, 78% specificity, and 89% accuracy. After linking the datasets, the completeness of key patient demographic information significantly improved, with missing race data reduced from 79% to 11% and missing ethnicity data from 82% to 17%. We designed the algorithm to be transparent and vendor neutral, making it potentially adaptable to any institution or practice regardless of their existing EHR/EDR systems. This provides a foundation for developing a clinical decision support systems that facilitate real-time health information exchange, supporting safer dental procedures, timely medical referrals, and integrative research. Our findings provide a critical bridge between medicine and dentistry, which have remained largely divorced from each other. Future work will focus on multi-institutional validation, implementation, and integration into routine clinical workflows.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"7 1","pages":"220345251383863"},"PeriodicalIF":7.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545351","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 Lichen Planus and Systemic Diseases.","authors":"S Warnakulasuriya,P Ramos-García,M Á González-Moles","doi":"10.1177/00220345251385966","DOIUrl":"https://doi.org/10.1177/00220345251385966","url":null,"abstract":"The mouth is referred to as \"the mirror of health and disease in the body.\" This review critically examines the comorbidity between systemic diseases and oral lichen planus, an autoimmune disorder affecting the oral mucosa with malignant potential and of high worldwide prevalence. Research has indicated that patients with oral lichen planus are significantly predisposed to diabetes mellitus (pooled proportion [PP] = 9.77%, odds ratio [OR] = 1.64, P < 0.001), Hashimoto thyroiditis (PP = 8.60%, OR = 2.2, P < 0.001), hypothyroidism (PP = 8.14%, OR = 1.65, P = 0.02), hyperthyroidism (PP = 2.84%, OR = 2.11, P = 0.007), celiac disease (PP = 7.14%, OR = 4.09, P < 0.001), hepatitis C (PP = 7.14%, OR = 4.09, P < 0.001), hepatitis B (PP = 3.90%, OR = 1.62, P = 0.02), steatohepatitis (PP = 7.06%, OR = 5.71, P = 0.05), liver cirrhosis (PP = 4.27%, OR = 5.8, P = 0.002), depression (PP = 31.19%, OR = 6.15, P < 0.001), anxiety (PP = 54.76%, OR = 3.51, P < 0.001), and stress (PP = 41.10%, OR = 3.64, P = 0.005). A good knowledge of these associations may assist primary care physicians, dentists, and other oral health professionals involved in the management of patients with oral lichen planus since many patients may be unaware of these associations and could have an impact on their general health. Some of these diseases, such as diabetes, have a role in the development of oral lichen planus. In addition, most of these comorbidities act as risk factors for cancer of different locations: liver, thyroid, small intestine, and the oral cavity. Current evidence indicates a high prevalence and a higher risk of systemic diseases in patients with oral lichen planus compared with the general population. Future research is recommended to increase our knowledge of pathobiology and clinical management of these associations.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"138 1","pages":"220345251385966"},"PeriodicalIF":7.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545353","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":"Letter to the Editor, “Early Childhood Exposures to Fluorides and Cognitive Neurodevelopment: A Population-Based Longitudinal Study”","authors":"C. Neurath, H. Limeback, C.V. Howard","doi":"10.1177/00220345251368276","DOIUrl":"https://doi.org/10.1177/00220345251368276","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"33 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509216","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":"Transcription Accuracy of Automatic Speech Recognition for Orthodontic Clinical Records","authors":"R. O’Kane, D. Stonehouse-Smith, L.C.U. Ota, R. Patel, N. Johnson, C. Slipper, J. Seehra, S.N. Papageorgiou, M.T. Cobourne","doi":"10.1177/00220345251382452","DOIUrl":"https://doi.org/10.1177/00220345251382452","url":null,"abstract":"Accurate clinical records are fundamental to dental practice. Automatic speech recognition (ASR) has the capacity to convert spoken clinical language into written text within the electronic health record; however, the accuracy of ASR in natural language processing for clinical dentistry remains uncertain. The aim of this study was to investigate the transcriptional accuracy of ASR systems using orthodontic clinical records as the experimental model. Specifically, we used 4 commercial ASR systems (Heidi Health, DigitalTCO, Dragon Medical One, Dragon Professional Anywhere), 5 application programming interfaces (Amazon, Google, Speechmatics, Whisper, GPT4oTranscribe), and a 2-stage pipeline coupling GPT4oTranscribe with the GPT4o large language model (LLM) for generative error correction (GPT4oTranscribeCorrected). Orthodontic diagnostic and treatment planning summaries ( &lt;jats:italic toggle=\"yes\"&gt;n&lt;/jats:italic&gt; = 200; 10 subject domains; 43,408 words; 6 h of audio) were narrated and recorded for analysis. The primary outcome was domain word error rate (DWER), which investigates clinical terminological transcription errors against the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) database. Secondary outcomes included nondomain WER (N-DWER), lexical accuracy (Recall-Oriented Understudy for Gisting Evaluation [ROUGE] score), semantic similarity (Bidirectional Encoder Representations from Transformers [BERT] and Bidirectional and Auto-Regressive Transformer [BART] scores), hallucinations (transcribed text not in the spoken input), and qualitative error analysis. GPT4oTranscribeCorrected was transcriptionally most accurate (DWER = 3.5%; WER = 3.7%), with DWER decreasing by 54.9% versus GPT4oTranscribe. Heidi Health was the highest-performing commercial system (DWER = 6.2%; WER = 5.4%), with Dragon Professional Anywhere being the worst (WER = 33.9%). All systems were less accurate with technical vocabulary (DWER &gt; N-DWER; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; &lt; 0.001), except GPT4oTranscribeCorrected. Significant differences were seen across systems for ROUGE, BERT, and BART scores ( &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; &lt; 0.001). Based on post hoc pairwise comparisons, GPT4oTranscribeCorrected performed best and Dragon Professional Anywhere was consistently worst for lexical and semantic errors. Hallucinations were absent except for Whisper ( &lt;jats:italic toggle=\"yes\"&gt;n&lt;/jats:italic&gt; = 57) and DigitalTCO ( &lt;jats:italic toggle=\"yes\"&gt;n&lt;/jats:italic&gt; = 1). Across systems, background noise increased DWER and WER ( &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; &lt; 0.001). Importantly, clinically significant errors were seen with all systems, ranging from 2% to 66% (GPT4oTranscribeCorrected clean; Dragon Medical One background noise, respectively). Variation in narrator accent had no effect in clean conditions ( &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; = 0.65) and a small effect with background noise ( &lt;jats:italic toggle=\"y","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"12 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427794","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":"Vasculogenic Precedes Neurogenic Differentiation in Dental Pulp Stem Cells","authors":"R. Tsuboi, Z. Zhang, K. Warner, S. The, E.T. Keller, J.E. Nör","doi":"10.1177/00220345251379776","DOIUrl":"https://doi.org/10.1177/00220345251379776","url":null,"abstract":"Dental pulp stem cells (DPSCs) are neural crest–derived stem cells endowed with multipotency and self-renewal. While processes orchestrating DPSC differentiation have been studied extensively, mechanisms underpinning the differentiation of human DPSCs <jats:italic toggle=\"yes\">in vivo</jats:italic> remain unclear. Here, we induced vasculogenic, odontoblastic, or neurogenic differentiation of human DPSCs for 7 d <jats:italic toggle=\"yes\">in vitro</jats:italic> and performed single-cell RNA sequencing. Then, human DPSCs tagged with green fluorescent protein (DPSC-GFP) seeded in human tooth slice/scaffolds were transplanted into the subcutaneous space of immunodeficient mice. DPSC-GFP were sorted by flow cytometry 7 and 21 d after transplantation, and single-cell RNA sequencing was performed. In addition, a time course study was performed to investigate the sequence of differentiation events triggered upon transplantation of DPSC-GFP into mice. Here, we observed 8 distinct clusters of DPSCs at baseline, indicating a high level of cell heterogeneity. When DPSCs were induced to undergo vasculogenic, odontoblastic, or neurogenic differentiation <jats:italic toggle=\"yes\">in vitro</jats:italic> , we observed distinct shifts in patterns of gene expression. Although some DPSCs retained mesenchymal stem cell markers likely due to asymmetric cell division and self-renewal, each differentiation protocol resulted in a unique gene expression signature. Stem cell markers that were highly expressed in DPSCs pretransplantation were progressively downregulated after 7 and 21 d in vivo. In contrast, endothelial cell markers presented high expression levels 7 d after transplantation, while neuronal markers showed upregulation 21 d after transplantation. Notably, while DPSC-derived functional blood vessels (i.e., blood-carrying vessels) can be clearly seen 2 wk after transplantation, well-defined DPSC-derived neural structures can be observed only after 5 wk. In conclusion, DPSCs are heterogeneous stem cells with distinct cell clusters, all of which contain progenitor cells with unique differentiation potential. Furthermore, this work demonstrated that microenvironment cues generated within human root canals are sufficient to induce vasculogenic differentiation, followed by neurogenic differentiation of DPSCs <jats:italic toggle=\"yes\">in vivo</jats:italic> .","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"64 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427764","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":"CaSR Activation Triggers Mandibular Overgrowth in Familial Mandibular Prognathism Patients and Mice.","authors":"H Fang,P Li,Y Wei,H Li,P Wang,X Yang,H Yu,Y Fan,S Zhu,R Bi","doi":"10.1177/00220345251384290","DOIUrl":"https://doi.org/10.1177/00220345251384290","url":null,"abstract":"Mandibular prognathism (MP) is the most common type of dentomaxillofacial deformity in East Asian populations. Genetic studies have revealed several MP-associated loci, suggesting that MP could be inherited as familial MP (fMP). However, functional verifications and in-depth mechanistic investigations of these loci are limited. For this study, we recruited 5 fMP families with 17 fMP members and 7 normal members. We first compared the clinical features of the 17 fMP members with 31 nonfamilial MP patients, finding a stronger mandibular overgrowth phenotype in the fMP subjects. Next, we performed whole-exome sequencing analysis with members of the 5 fMP families and singled out a potential fMP-associated pathogenic variant in the CASR gene (namely, rs117375173); the mutation introduces an amino acid substitution (A601G) in exon 7 and confers gain of function in Calcium-Sensing Receptor (CaSR). The rs11735173 variant changes the CaSR protein structure toward a semiactive state, similar to CaSR activated by L-tryptophan (L-Trp). To verify the regulating roles of CASR in mandibular bone growth, we further generated different mouse models with abnormal CaSR function. L-Trp administration effectively activated CaSR/GNAQ expression in vivo and in vitro. The MC3T3-E1 cell line transfected with CaSR with rs117375173 (CaSRA601G) showed increased osteogenic differentiation and collagen synthesis at the transcriptional level. Local injection of L-Trp in the mandible of growing mice significantly increased the mandibular length and BMD, due to activated osteogenic activity and suppressed bone resorption. At the same time, loss of function of CaSR in osteogenic progenitors caused mandibular growth retardation in Gli1-CreER; Casrfl/fl; tdTomatofl/+ mice. In conclusion, our study reveals that abnormal functioning of CaSR affects mandibular bone development and may contribute to the pathogenesis of fMP, providing a theoretical and experimental basis for the early diagnosis of and therapeutic strategies for fMP in clinical practice.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"125 1","pages":"220345251384290"},"PeriodicalIF":7.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145434014","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":"CD300lf Regulates Neutrophil Aging and Periodontal Immune Homeostasis","authors":"Z. Zou, J. Guo, J. Li, Y. Bao, W. Xie, Q. Hu, L. Wen, H. Lu, X. Liu, Q. Dong, J. Fang, Q. Hu, Y. Cao, Z. Wang, L. Yang, X. Wang","doi":"10.1177/00220345251382572","DOIUrl":"https://doi.org/10.1177/00220345251382572","url":null,"abstract":"Immune alterations, such as neutrophil dysfunction, significantly affect the progression and outcome of periodontitis, a prevalent inflammatory disease. Despite this, the molecular mechanisms driving neutrophil dysregulation in periodontitis remain poorly understood. In this study, we demonstrate that CD300lf, a critical immune regulator, is markedly downregulated in neutrophils from a periodontitis mouse model and human patients. The loss of CD300lf accelerates neutrophil aging, as evidenced by increased reactive oxygen species production, the senescence-associated secretory phenotype with elevated IL-1β and S100A8/A9 levels, and heightened neutrophil extracellular trap formation. Mechanistically, CD300lf deficiency leads to MyD88 upregulation, indicating a shift toward a proinflammatory state. Inhibition of MyD88 effectively reduces periodontal inflammation in CD300lf-deficient mice. Furthermore, targeting CD300lf with its known ligand ceramide alleviates periodontitis and mitigates the aging phenotype of neutrophils. These findings underscore the critical role of the CD300lf/MyD88 axis in neutrophil homeostasis and suggest that modulation of CD300lf through ceramide presents a promising therapeutic strategy for periodontitis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"1 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427763","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}