Pub Date : 2026-03-15DOI: 10.1177/00220345261424242
M-X Li,W-H Deng,Z-X Wu,C-X Jin,J-M Wu,Y Han,J K H Tsoi,G-S Xia,C Huang
Vision-language models (VLMs) have demonstrated significant potential in medical image analysis, yet their application in intraoral photography remains largely underexplored due to the lack of fine-grained, annotated datasets and comprehensive benchmarks. To address this, we present MetaDent, a comprehensive resource that includes 1) a novel and large-scale dentistry image dataset collected from clinical, public, and web sources; 2) a semistructured annotation framework designed to capture the hierarchical and clinically nuanced nature of dental photography; and 3) comprehensive benchmark suites for evaluating state-of-the-art VLMs on clinical image understanding. Our labeling approach combines a high-level image summary with point-by-point, free-text descriptions of abnormalities. This method enables rich, scalable, and task-agnostic representations. We curated 60,669 dental images from diverse sources and annotated a representative subset of 2,588 images using this meta-labeling scheme. Leveraging large language models (LLMs), we derive standardized benchmarks: approximately 15,000 visual question answering (VQA) pairs and an 18-class multilabel classification dataset, which we validated with human review and error analysis to justify that the LLM-driven transition reliably preserves fidelity and semantic accuracy. We then evaluate state-of-the-art VLMs across VQA, classification, and image captioning tasks. Quantitative results reveal that even the most advanced models struggle with a fine-grained understanding of intraoral scenes, achieving moderate accuracy (e.g., less than 70% in VQA) and producing inconsistent or incomplete descriptions in image captioning. These findings underscore the gap between general-purpose VLMs and the demands of specialized models, highlighting the need for domain-adapted training and more sophisticated evaluation protocols to assist professional dental practice and community oral health efforts. We publicly release our dataset, annotations, and tools to foster reproducible research and accelerate the development of vision-language systems for dental applications.
{"title":"MetaDent: Labeling Clinical Images for Vision-Language Models in Dentistry.","authors":"M-X Li,W-H Deng,Z-X Wu,C-X Jin,J-M Wu,Y Han,J K H Tsoi,G-S Xia,C Huang","doi":"10.1177/00220345261424242","DOIUrl":"https://doi.org/10.1177/00220345261424242","url":null,"abstract":"Vision-language models (VLMs) have demonstrated significant potential in medical image analysis, yet their application in intraoral photography remains largely underexplored due to the lack of fine-grained, annotated datasets and comprehensive benchmarks. To address this, we present MetaDent, a comprehensive resource that includes 1) a novel and large-scale dentistry image dataset collected from clinical, public, and web sources; 2) a semistructured annotation framework designed to capture the hierarchical and clinically nuanced nature of dental photography; and 3) comprehensive benchmark suites for evaluating state-of-the-art VLMs on clinical image understanding. Our labeling approach combines a high-level image summary with point-by-point, free-text descriptions of abnormalities. This method enables rich, scalable, and task-agnostic representations. We curated 60,669 dental images from diverse sources and annotated a representative subset of 2,588 images using this meta-labeling scheme. Leveraging large language models (LLMs), we derive standardized benchmarks: approximately 15,000 visual question answering (VQA) pairs and an 18-class multilabel classification dataset, which we validated with human review and error analysis to justify that the LLM-driven transition reliably preserves fidelity and semantic accuracy. We then evaluate state-of-the-art VLMs across VQA, classification, and image captioning tasks. Quantitative results reveal that even the most advanced models struggle with a fine-grained understanding of intraoral scenes, achieving moderate accuracy (e.g., less than 70% in VQA) and producing inconsistent or incomplete descriptions in image captioning. These findings underscore the gap between general-purpose VLMs and the demands of specialized models, highlighting the need for domain-adapted training and more sophisticated evaluation protocols to assist professional dental practice and community oral health efforts. We publicly release our dataset, annotations, and tools to foster reproducible research and accelerate the development of vision-language systems for dental applications.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"100 1","pages":"220345261424242"},"PeriodicalIF":7.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461776","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}
Pub Date : 2026-03-15DOI: 10.1177/00220345251414354
A Sandell,M Giacomini,M Risteli,S Kilpinen,T Salo,A Al-Samadi
Oral epithelial dysplasia (OED) is characterized by abnormal structural and cellular changes in the oral mucosa epithelium. These changes are often detected histologically in potentially malignant disorders and are associated with an increased risk of malignant transformation into oral squamous cell carcinoma (OSCC). Currently, clinicians rely mainly on the pathologist's histological gradings (binary or tertiary grading systems) to determine the follow-up protocol for patients with OED. However, both histological gradings are rather subjective and not highly reliable. Therefore, there is a need for biomarkers to distinguish high-risk OED cases from low-risk cases. Twelve oral tongue dysplasia samples were collected for multiplex immunostaining. The samples were derived from 7 patients who did not develop OSCC within 5 y of their OED diagnosis (low-risk group, LR) and 5 patients who developed OSCC (high-risk group, HR). Ten antibodies targeting epithelial cells, immune cells, a proliferation marker, and immune checkpoints were used (PanCK, CD4, CD8, CD11b, CD68, CD56, FoxP3, Ki67, PD-1, PD-L1). Uniform manifold approximation and projection generated from multiplex staining revealed distinct differences in the distribution of immune cells and immune checkpoint expression between the LR and HR groups. The HR group showed a higher number of CD8+ cytotoxic T cells and CD68+ macrophages than the LR group. Notably, both PanCK+ epithelial cells and CD8+ cytotoxic T cells exhibited increased proliferation in the HR group, as indicated by Ki67 expression. Additionally, PD-1 expression was significantly elevated in the HR group. The logistics regression model further confirmed the predictive value of individual markers and identified a multimarker model with superior predictive performance. Our multiplex immunostaining revealed significant differences in the immune landscape between LR and HR cases of OED dysplasia. CD8+ cytotoxic T cells, CD68+ macrophages, and PD-1+ cells may serve as potential biomarkers for stratifying HR from LR oral tongue dysplasia cases.
{"title":"Immune Landscape Reveals Biomarkers for High-Risk Oral Tongue Dysplasia.","authors":"A Sandell,M Giacomini,M Risteli,S Kilpinen,T Salo,A Al-Samadi","doi":"10.1177/00220345251414354","DOIUrl":"https://doi.org/10.1177/00220345251414354","url":null,"abstract":"Oral epithelial dysplasia (OED) is characterized by abnormal structural and cellular changes in the oral mucosa epithelium. These changes are often detected histologically in potentially malignant disorders and are associated with an increased risk of malignant transformation into oral squamous cell carcinoma (OSCC). Currently, clinicians rely mainly on the pathologist's histological gradings (binary or tertiary grading systems) to determine the follow-up protocol for patients with OED. However, both histological gradings are rather subjective and not highly reliable. Therefore, there is a need for biomarkers to distinguish high-risk OED cases from low-risk cases. Twelve oral tongue dysplasia samples were collected for multiplex immunostaining. The samples were derived from 7 patients who did not develop OSCC within 5 y of their OED diagnosis (low-risk group, LR) and 5 patients who developed OSCC (high-risk group, HR). Ten antibodies targeting epithelial cells, immune cells, a proliferation marker, and immune checkpoints were used (PanCK, CD4, CD8, CD11b, CD68, CD56, FoxP3, Ki67, PD-1, PD-L1). Uniform manifold approximation and projection generated from multiplex staining revealed distinct differences in the distribution of immune cells and immune checkpoint expression between the LR and HR groups. The HR group showed a higher number of CD8+ cytotoxic T cells and CD68+ macrophages than the LR group. Notably, both PanCK+ epithelial cells and CD8+ cytotoxic T cells exhibited increased proliferation in the HR group, as indicated by Ki67 expression. Additionally, PD-1 expression was significantly elevated in the HR group. The logistics regression model further confirmed the predictive value of individual markers and identified a multimarker model with superior predictive performance. Our multiplex immunostaining revealed significant differences in the immune landscape between LR and HR cases of OED dysplasia. CD8+ cytotoxic T cells, CD68+ macrophages, and PD-1+ cells may serve as potential biomarkers for stratifying HR from LR oral tongue dysplasia cases.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"10 1","pages":"220345251414354"},"PeriodicalIF":7.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461777","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}
Pub Date : 2026-03-08DOI: 10.1177/00220345261416502
C Wetzel,C V Bumm,J Becker,F Schwendicke,M Folwaczny,N Werner
Infertility is an increasing global health concern. Growing evidence suggests that systemic inflammatory conditions, including periodontal disease, may contribute to impaired reproductive outcomes. This narrative review highlights recent conceptual advances linking periodontal disease with male and female infertility, focusing on biological mechanisms (i.e., microbial translocation, chronic inflammation, immune dysregulation, oxidative stress, and epigenetic modifications). The review critically examines available studies focusing on scientific quality, design, and clinical relevance. In females, periodontal disease has been associated with idiopathic infertility and polycystic ovary syndrome. These conditions are characterized by immune dysregulation and low-grade systemic inflammation. In males, impaired semen parameters and idiopathic infertility have been linked to poor periodontal status. Despite growing interest, existing studies are largely associative and limited by methodological heterogeneity, insufficient control for confounders, and a lack of standardized outcome measures. This review proposes a framework for improved future research strategies addressing these shortcomings to clarify causality and therapeutic potential.
{"title":"Infertility and Periodontitis: Are We Connecting the Right Dots?","authors":"C Wetzel,C V Bumm,J Becker,F Schwendicke,M Folwaczny,N Werner","doi":"10.1177/00220345261416502","DOIUrl":"https://doi.org/10.1177/00220345261416502","url":null,"abstract":"Infertility is an increasing global health concern. Growing evidence suggests that systemic inflammatory conditions, including periodontal disease, may contribute to impaired reproductive outcomes. This narrative review highlights recent conceptual advances linking periodontal disease with male and female infertility, focusing on biological mechanisms (i.e., microbial translocation, chronic inflammation, immune dysregulation, oxidative stress, and epigenetic modifications). The review critically examines available studies focusing on scientific quality, design, and clinical relevance. In females, periodontal disease has been associated with idiopathic infertility and polycystic ovary syndrome. These conditions are characterized by immune dysregulation and low-grade systemic inflammation. In males, impaired semen parameters and idiopathic infertility have been linked to poor periodontal status. Despite growing interest, existing studies are largely associative and limited by methodological heterogeneity, insufficient control for confounders, and a lack of standardized outcome measures. This review proposes a framework for improved future research strategies addressing these shortcomings to clarify causality and therapeutic potential.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"85 1","pages":"220345261416502"},"PeriodicalIF":7.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374027","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}
Pub Date : 2026-03-08DOI: 10.1177/00220345251411887
J Zhou,F Shen,C You,M Liu,X Xie,L Zhao,L Ye,J Wang,Y Shi
The precise cellular origin and regulatory mechanisms underlying cementum development remain poorly understood, hindering progress toward ideal cementum regeneration. Bone morphogenetic protein 2 (BMP2), approved by the US Food and Drug Administration for clinical use due to its potent osteoinductive capacity, is a key candidate for such regulation. Activin receptor-like kinase 3 (Alk3)-mediated BMP signaling plays a crucial role in the development and structural maintenance of mineralized tissues, including teeth. However, the precise mechanism by which BMP signaling regulates periodontal tissue development mediated by periodontal ligament stem cells (PDLSCs), especially Gli1+ cells, remains unknown. Emerging evidence has indicated that O-GlcNAc glycosylation (O-GlcNAcylation), a dynamic posttranslational modification, modulates critical biological processes, such as transcription, translation, and cell fate determination. In this study, we demonstrate how BMP2 signaling enhances O-GlcNAcylation in a SMAD-dependent manner. Notably, we demonstrate that the lack of Alk3 in Gli1+ cells resulted in reduced O-GlcNAcylation levels in vivo. Nonetheless, O-GlcNAcylation is identified as indispensable for PDLSC-mediated osteogenesis and cementogenesis both in vivo and in vitro. Moreover, deleting O-β-N-acetylglucosaminyltransferase (Ogt) in Gli1+ cells suppresses BMP signaling, consequently impairing cellular cementum formation and delaying alveolar socket healing. Mechanistically, we further revealed that the cytoskeleton, especially MYH9 (nonmuscle myosin IIA, NMIIA), is O-GlcNAcylated and is essential for BMP2-induced osteogenic/cementogenic differentiation. These findings demonstrate that O-GlcNAcylation is essential for cellular cementum formation by modulating the BMP signaling pathway in PDLSC differentiation and Gli1+ periodontal progenitors, highlighting its critical role in both tooth root development and alveolar bone repair.
{"title":"O-GlcNAcylation Mediates BMP2-Induced Osteogenesis/Cementogenesis via NMIIA.","authors":"J Zhou,F Shen,C You,M Liu,X Xie,L Zhao,L Ye,J Wang,Y Shi","doi":"10.1177/00220345251411887","DOIUrl":"https://doi.org/10.1177/00220345251411887","url":null,"abstract":"The precise cellular origin and regulatory mechanisms underlying cementum development remain poorly understood, hindering progress toward ideal cementum regeneration. Bone morphogenetic protein 2 (BMP2), approved by the US Food and Drug Administration for clinical use due to its potent osteoinductive capacity, is a key candidate for such regulation. Activin receptor-like kinase 3 (Alk3)-mediated BMP signaling plays a crucial role in the development and structural maintenance of mineralized tissues, including teeth. However, the precise mechanism by which BMP signaling regulates periodontal tissue development mediated by periodontal ligament stem cells (PDLSCs), especially Gli1+ cells, remains unknown. Emerging evidence has indicated that O-GlcNAc glycosylation (O-GlcNAcylation), a dynamic posttranslational modification, modulates critical biological processes, such as transcription, translation, and cell fate determination. In this study, we demonstrate how BMP2 signaling enhances O-GlcNAcylation in a SMAD-dependent manner. Notably, we demonstrate that the lack of Alk3 in Gli1+ cells resulted in reduced O-GlcNAcylation levels in vivo. Nonetheless, O-GlcNAcylation is identified as indispensable for PDLSC-mediated osteogenesis and cementogenesis both in vivo and in vitro. Moreover, deleting O-β-N-acetylglucosaminyltransferase (Ogt) in Gli1+ cells suppresses BMP signaling, consequently impairing cellular cementum formation and delaying alveolar socket healing. Mechanistically, we further revealed that the cytoskeleton, especially MYH9 (nonmuscle myosin IIA, NMIIA), is O-GlcNAcylated and is essential for BMP2-induced osteogenic/cementogenic differentiation. These findings demonstrate that O-GlcNAcylation is essential for cellular cementum formation by modulating the BMP signaling pathway in PDLSC differentiation and Gli1+ periodontal progenitors, highlighting its critical role in both tooth root development and alveolar bone repair.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"58 1","pages":"220345251411887"},"PeriodicalIF":7.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374030","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}
Pub Date : 2026-03-08DOI: 10.1177/00220345261416826
N Z Bashir,C C K Chan,C McGrath
Timely dental care is essential for children's health and development, yet disparities persist, particularly among immigrants and children of immigrants. This study examined how children's and their parents' immigration status affects dental care utilization, considering social capital and material hardship as mediators. Using 8 waves of the National Survey of Children's Health from 2016 through 2023, we analyzed a nationally representative, pooled, cross-sectional survey sample of 274,302 children in the United States aged 2 to 17 y. Latent variables for social capital, material hardship, and socioeconomic status (SES) were constructed from factor analysis of observable indicators. Multivariable structural equation models simultaneously included child and parental immigration status as exposures to assess pathways linking immigration to dental attendance and receipt of preventive dental care. We compared models with mediation versus confounding by SES. Results indicate that social capital is a primary pathway through which immigration status reduces dental attendance. Social capital mediated the effect of being a foreign-born child in both the mediation-by-SES and confounding-by-SES models (odds ratio [OR], 0.74; 95% confidence intervals [CI], 0.64-0.86). Similarly, social capital mediated the effect of having foreign-born parents in both models (OR, 0.59; 95% CI, 0.46-0.76). Comparing the pathways of the 2 exposures revealed heterogeneity: direct effects (i.e., those not mediated by social capital or material hardship) were stronger than mediated effects for the child's immigrant status, whereas mediated effects were stronger for parental immigrant status. Our findings remained consistent when assessing receipt of preventive care as an outcome and also when carrying out sensitivity analyses comparing the pre- and post-COVID-19 periods. These results highlight social capital as a potential target for future research into reducing dental care disparities among immigrant children. Improving social networks, community engagement, and access to supportive resources may potentially be a viable way to promote equitable utilization of dental care.
{"title":"Pathways Mediating Immigration and Utilization of Dental Care in Children.","authors":"N Z Bashir,C C K Chan,C McGrath","doi":"10.1177/00220345261416826","DOIUrl":"https://doi.org/10.1177/00220345261416826","url":null,"abstract":"Timely dental care is essential for children's health and development, yet disparities persist, particularly among immigrants and children of immigrants. This study examined how children's and their parents' immigration status affects dental care utilization, considering social capital and material hardship as mediators. Using 8 waves of the National Survey of Children's Health from 2016 through 2023, we analyzed a nationally representative, pooled, cross-sectional survey sample of 274,302 children in the United States aged 2 to 17 y. Latent variables for social capital, material hardship, and socioeconomic status (SES) were constructed from factor analysis of observable indicators. Multivariable structural equation models simultaneously included child and parental immigration status as exposures to assess pathways linking immigration to dental attendance and receipt of preventive dental care. We compared models with mediation versus confounding by SES. Results indicate that social capital is a primary pathway through which immigration status reduces dental attendance. Social capital mediated the effect of being a foreign-born child in both the mediation-by-SES and confounding-by-SES models (odds ratio [OR], 0.74; 95% confidence intervals [CI], 0.64-0.86). Similarly, social capital mediated the effect of having foreign-born parents in both models (OR, 0.59; 95% CI, 0.46-0.76). Comparing the pathways of the 2 exposures revealed heterogeneity: direct effects (i.e., those not mediated by social capital or material hardship) were stronger than mediated effects for the child's immigrant status, whereas mediated effects were stronger for parental immigrant status. Our findings remained consistent when assessing receipt of preventive care as an outcome and also when carrying out sensitivity analyses comparing the pre- and post-COVID-19 periods. These results highlight social capital as a potential target for future research into reducing dental care disparities among immigrant children. Improving social networks, community engagement, and access to supportive resources may potentially be a viable way to promote equitable utilization of dental care.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"298 1","pages":"220345261416826"},"PeriodicalIF":7.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374094","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}
Lymphatic vessels play a pivotal role in tissue homeostasis and repair, yet their function in periodontal healing remains poorly defined. In this study, we investigated the spatial dynamics and functional significance of lymphatics during periodontal wound repair using a mouse model of ligature-induced periodontitis. By combining Prox1-tdTomato transgenic reporter mice with advanced tissue clearing and light sheet microscopy, we generated high-resolution 3-dimensional images of gingival lymphatic networks under both physiological and repair conditions. Our observations revealed that lymphatic vessels undergo active and spatially organized reassembly during the healing phase. Notably, we found a region-specific increase in lymphatic branching and density in the marginal gingiva, suggesting localized lymphangiogenesis. Time course analysis confirmed that this lymphatic remodeling peaks during the granulation tissue formation phase. We further identified epithelial upregulation of Vegfc during the repair phase and demonstrated that local administration of vascular endothelial growth factor C (VEGF-C) C156S, a VEGFR-3-specific agonist, enhanced lymphatic vessel function and alveolar bone repair. To explore the underlying molecular mechanisms, we successfully established, for the first time, primary cultures of gingiva-derived lymphatic endothelial cells (LECs). Comparative transcriptomic analysis revealed distinct signatures of gingival LECs compared to lymph node or dermal LECs. These cells maintained typical LEC characteristics in vitro and responded robustly to VEGF-C stimulation. RNA sequencing and functional apoptosis assays revealed significant modulation of apoptosis-related genes, including downregulation of Ell3 and upregulation of Siah1b, suggesting a survival-promoting role for VEGF-C signaling in LECs. Collectively, our findings highlight a previously underappreciated regenerative role of lymphatic vessels in the periodontium and establish lymphangiogenic activation as a potential therapeutic strategy for enhancing periodontal repair. The successful culture of primary gingival LECs further provides a novel platform for mechanistic studies in oral lymphatic biology.
{"title":"VEGF-C-Driven Lymphatic Survival Signaling Promotes Periodontal Repair.","authors":"S Matsumoto,T Iwayama,P Bhongsatiern,Y Yoshida,Y Koketsu,E Tsuboi,S Takashiba,Y Sato,S Murakami,M Takedachi","doi":"10.1177/00220345261421161","DOIUrl":"https://doi.org/10.1177/00220345261421161","url":null,"abstract":"Lymphatic vessels play a pivotal role in tissue homeostasis and repair, yet their function in periodontal healing remains poorly defined. In this study, we investigated the spatial dynamics and functional significance of lymphatics during periodontal wound repair using a mouse model of ligature-induced periodontitis. By combining Prox1-tdTomato transgenic reporter mice with advanced tissue clearing and light sheet microscopy, we generated high-resolution 3-dimensional images of gingival lymphatic networks under both physiological and repair conditions. Our observations revealed that lymphatic vessels undergo active and spatially organized reassembly during the healing phase. Notably, we found a region-specific increase in lymphatic branching and density in the marginal gingiva, suggesting localized lymphangiogenesis. Time course analysis confirmed that this lymphatic remodeling peaks during the granulation tissue formation phase. We further identified epithelial upregulation of Vegfc during the repair phase and demonstrated that local administration of vascular endothelial growth factor C (VEGF-C) C156S, a VEGFR-3-specific agonist, enhanced lymphatic vessel function and alveolar bone repair. To explore the underlying molecular mechanisms, we successfully established, for the first time, primary cultures of gingiva-derived lymphatic endothelial cells (LECs). Comparative transcriptomic analysis revealed distinct signatures of gingival LECs compared to lymph node or dermal LECs. These cells maintained typical LEC characteristics in vitro and responded robustly to VEGF-C stimulation. RNA sequencing and functional apoptosis assays revealed significant modulation of apoptosis-related genes, including downregulation of Ell3 and upregulation of Siah1b, suggesting a survival-promoting role for VEGF-C signaling in LECs. Collectively, our findings highlight a previously underappreciated regenerative role of lymphatic vessels in the periodontium and establish lymphangiogenic activation as a potential therapeutic strategy for enhancing periodontal repair. The successful culture of primary gingival LECs further provides a novel platform for mechanistic studies in oral lymphatic biology.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"47 1","pages":"220345261421161"},"PeriodicalIF":7.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374147","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}
Pub Date : 2026-03-08DOI: 10.1177/00220345261416506
H Zhang,X Mao,S Ge,B Ma
Periodontitis is characterized by bacterial infection, elevated reactive oxygen species (ROS), excessive inflammation, and immune imbalance. Consequently, there is an urgent need to devise promising strategies capable of simultaneously combating infection, alleviating oxidative stress, suppressing inflammation, and regulating immunity in periodontitis management. Herein, an injectable silk fibroin/quercetin (SFQ) natural hydrogel was developed through self-assembly. The quercetin-silk fibroin interaction and the quercetin-enhanced β-sheet formed the self-assembled dual-network structure, bringing good injectability and mechanical stability. SFQ hydrogel with high biocompatibility promoted cell migration, scavenged ROS, relieved mitochondrial damage, and prevented cellular apoptosis. Meanwhile, SFQ hydrogel possessed a satisfactory anti-inflammatory ability and regulated immune response by inhibiting M1 polarization and promoting M2 polarization of macrophages. In addition, SFQ hydrogel can efficiently kill free bacteria and inhibit biofilm formation. In vivo experiments revealed that SFQ hydrogel significantly ameliorated inflammation, reduced collagen destruction, and regulated the immune micro milieu for tissue remodeling. Overall, self-assembled SFQ natural hydrogel offers a promising therapeutic option for improving the treatment of periodontitis.
{"title":"Dual-Network Silk Fibroin/Quercetin Hydrogel for Periodontitis Treatment.","authors":"H Zhang,X Mao,S Ge,B Ma","doi":"10.1177/00220345261416506","DOIUrl":"https://doi.org/10.1177/00220345261416506","url":null,"abstract":"Periodontitis is characterized by bacterial infection, elevated reactive oxygen species (ROS), excessive inflammation, and immune imbalance. Consequently, there is an urgent need to devise promising strategies capable of simultaneously combating infection, alleviating oxidative stress, suppressing inflammation, and regulating immunity in periodontitis management. Herein, an injectable silk fibroin/quercetin (SFQ) natural hydrogel was developed through self-assembly. The quercetin-silk fibroin interaction and the quercetin-enhanced β-sheet formed the self-assembled dual-network structure, bringing good injectability and mechanical stability. SFQ hydrogel with high biocompatibility promoted cell migration, scavenged ROS, relieved mitochondrial damage, and prevented cellular apoptosis. Meanwhile, SFQ hydrogel possessed a satisfactory anti-inflammatory ability and regulated immune response by inhibiting M1 polarization and promoting M2 polarization of macrophages. In addition, SFQ hydrogel can efficiently kill free bacteria and inhibit biofilm formation. In vivo experiments revealed that SFQ hydrogel significantly ameliorated inflammation, reduced collagen destruction, and regulated the immune micro milieu for tissue remodeling. Overall, self-assembled SFQ natural hydrogel offers a promising therapeutic option for improving the treatment of periodontitis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"40 1","pages":"220345261416506"},"PeriodicalIF":7.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374211","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}
Pub Date : 2026-03-08DOI: 10.1177/00220345261423834
R A Kamath,A Phanrungsuwan,C Ge,S Shahid,F F Mohamed,J Chung,Y Han,M Killian,V Kaartinen,B L Foster,R T Franceschi
Discoidin Domain Receptor 2 (DDR2) is a collagen-activated tyrosine kinase required for bone and tooth development as well as regeneration of calvarial and long bones. Although DDR2 is expressed in alveolar bone, its functions in this site have not been previously examined. The present study used global and conditional knockout approaches and lineage tracing to examine the functions of DDR2 in alveolar bone formation during tooth socket healing. First molars were extracted from the maxillae of wild-type and globally Ddr2-deficient (Ddr2LacZ/LacZ) mice, and socket healing was measured after 1, 2, or 4 wk. At all times, Ddr2 inactivation significantly reduced socket healing. These changes were associated with decreased cell proliferation 3 d after extraction without any detectable changes in apoptosis. In addition, collagen fibril orientation, measured using Picrosirius Red staining under polarized light, was disrupted in tooth sockets from Ddr2-deficient mice. For lineage tracing, 4-wk-old Ddr2mer-cre-mer; R26RtdTomato and Gli1CreERT2; R26RtdTomato mice were induced with tamoxifen, first molars were extracted, and socket healing was examined after 1, 3, or 7 d. In both cases, tdTomato+ cells migrated into sockets, where they sequentially co-localized with preosteoblast and osteoblast markers. Thus, both DDR2+ and GLI1+ cells contribute to socket healing. The considerable overlap observed between DDR2+ and GLI1+ cells suggested that DDR2 functioned in GLI1+ cells, which are known to have skeletal progenitor properties. Consistent with localization data, conditional knockout (Gli1CreERT2; Ddr2fl/fl) mice exhibited reductions in socket healing 1 wk postextraction, although the inhibition of socket repair was less than that seen in global Ddr2 knockouts. In summary, this work demonstrates a role for DDR2 in alveolar bone repair, a finding that may have therapeutic implications for the treatment of alveolar bone loss associated with periodontal disease and other disorders.
{"title":"Discoidin Domain Receptor 2 Is Required for Tooth Extraction Socket Healing.","authors":"R A Kamath,A Phanrungsuwan,C Ge,S Shahid,F F Mohamed,J Chung,Y Han,M Killian,V Kaartinen,B L Foster,R T Franceschi","doi":"10.1177/00220345261423834","DOIUrl":"https://doi.org/10.1177/00220345261423834","url":null,"abstract":"Discoidin Domain Receptor 2 (DDR2) is a collagen-activated tyrosine kinase required for bone and tooth development as well as regeneration of calvarial and long bones. Although DDR2 is expressed in alveolar bone, its functions in this site have not been previously examined. The present study used global and conditional knockout approaches and lineage tracing to examine the functions of DDR2 in alveolar bone formation during tooth socket healing. First molars were extracted from the maxillae of wild-type and globally Ddr2-deficient (Ddr2LacZ/LacZ) mice, and socket healing was measured after 1, 2, or 4 wk. At all times, Ddr2 inactivation significantly reduced socket healing. These changes were associated with decreased cell proliferation 3 d after extraction without any detectable changes in apoptosis. In addition, collagen fibril orientation, measured using Picrosirius Red staining under polarized light, was disrupted in tooth sockets from Ddr2-deficient mice. For lineage tracing, 4-wk-old Ddr2mer-cre-mer; R26RtdTomato and Gli1CreERT2; R26RtdTomato mice were induced with tamoxifen, first molars were extracted, and socket healing was examined after 1, 3, or 7 d. In both cases, tdTomato+ cells migrated into sockets, where they sequentially co-localized with preosteoblast and osteoblast markers. Thus, both DDR2+ and GLI1+ cells contribute to socket healing. The considerable overlap observed between DDR2+ and GLI1+ cells suggested that DDR2 functioned in GLI1+ cells, which are known to have skeletal progenitor properties. Consistent with localization data, conditional knockout (Gli1CreERT2; Ddr2fl/fl) mice exhibited reductions in socket healing 1 wk postextraction, although the inhibition of socket repair was less than that seen in global Ddr2 knockouts. In summary, this work demonstrates a role for DDR2 in alveolar bone repair, a finding that may have therapeutic implications for the treatment of alveolar bone loss associated with periodontal disease and other disorders.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"9 1","pages":"220345261423834"},"PeriodicalIF":7.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374024","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}
Pub Date : 2026-03-08DOI: 10.1177/00220345261425669
H Fischer,S Listl
Community water fluoridation (CWF) has become one of the most contested public health interventions despite a robust evidence base supporting its effectiveness, safety, and equity. Drawing on a recent comprehensive review, this perspective argues that persistent controversies revolve not only around the effectiveness, safety, and implementation of CWF but also around a "fourth controversy": how people evaluate and hold confidence in what they think they know. We discuss CWF as a case of contested science in which polarization and misinformation undermine belief updating. Using insights from metacognition research, we suggest that improving public reasoning requires communication and policy approaches that foster epistemic humility, iterative learning, and evidence-informed revision rather than reliance on evidence accumulation alone.
{"title":"Metacognition and Contested Science: The Case of Water Fluoridation.","authors":"H Fischer,S Listl","doi":"10.1177/00220345261425669","DOIUrl":"https://doi.org/10.1177/00220345261425669","url":null,"abstract":"Community water fluoridation (CWF) has become one of the most contested public health interventions despite a robust evidence base supporting its effectiveness, safety, and equity. Drawing on a recent comprehensive review, this perspective argues that persistent controversies revolve not only around the effectiveness, safety, and implementation of CWF but also around a \"fourth controversy\": how people evaluate and hold confidence in what they think they know. We discuss CWF as a case of contested science in which polarization and misinformation undermine belief updating. Using insights from metacognition research, we suggest that improving public reasoning requires communication and policy approaches that foster epistemic humility, iterative learning, and evidence-informed revision rather than reliance on evidence accumulation alone.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"82 1","pages":"220345261425669"},"PeriodicalIF":7.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374029","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}
Pub Date : 2026-03-08DOI: 10.1177/00220345251414409
E Petrauskiene,P Zaninotto,A Heilmann,A Peasey,G Tsakos
Associations between tooth loss and frailty have been reported, but longitudinal evidence on directionality and pathways of this association is lacking. We examined the direction and pathways of the association between edentulousness and frailty among older adults in England using a nationally representative sample of 6,800 adults aged ≥50 y who participated in the English Longitudinal Study of Ageing (ELSA) at wave 3. Edentulousness and frailty (determined using the Frailty Index) were assessed at waves 3 (2006/7), 5 (2010/11), and 7 (2014/15). The following mediators were assessed at waves 4 (2008/9) and 6 (2012/13): loneliness (UCLA Loneliness Scale), C-reactive protein (CRP), and consumption of fruit and vegetables. A cross-lagged longitudinal structural equation model with a Bayesian estimator using probit regression assessed the direction and pathways of the association between edentulousness and frailty at 2 time points (i.e., wave 3 to wave 5 and wave 5 to wave 7), after adjusting for sociodemographic factors and smoking. Being edentate at wave 3 was associated with an increased probability of frailty at wave 5, but the path was not significant between waves 5 and 7 (probit regression coefficient 0.05; 95% CI, -0.02 to 0.13). The paths from frailty to edentulousness were not significant at either time point (probit regression coefficients 0.09 [95% CI, -0.10 to 0.279] and 0.14 [95% CI, -0.03 to 0.31] for waves 3-5 and waves 5-7, respectively). The estimates of indirect paths via loneliness and CRP were of small magnitude but significant at both time points. No significant mediation was observed via the consumption of fruit and vegetables. Health promotion strategies aimed at preserving natural teeth and tackling loneliness in older people may have the potential to prevent frailty.
{"title":"Edentulousness and Frailty: A Study of Directionality and Pathways.","authors":"E Petrauskiene,P Zaninotto,A Heilmann,A Peasey,G Tsakos","doi":"10.1177/00220345251414409","DOIUrl":"https://doi.org/10.1177/00220345251414409","url":null,"abstract":"Associations between tooth loss and frailty have been reported, but longitudinal evidence on directionality and pathways of this association is lacking. We examined the direction and pathways of the association between edentulousness and frailty among older adults in England using a nationally representative sample of 6,800 adults aged ≥50 y who participated in the English Longitudinal Study of Ageing (ELSA) at wave 3. Edentulousness and frailty (determined using the Frailty Index) were assessed at waves 3 (2006/7), 5 (2010/11), and 7 (2014/15). The following mediators were assessed at waves 4 (2008/9) and 6 (2012/13): loneliness (UCLA Loneliness Scale), C-reactive protein (CRP), and consumption of fruit and vegetables. A cross-lagged longitudinal structural equation model with a Bayesian estimator using probit regression assessed the direction and pathways of the association between edentulousness and frailty at 2 time points (i.e., wave 3 to wave 5 and wave 5 to wave 7), after adjusting for sociodemographic factors and smoking. Being edentate at wave 3 was associated with an increased probability of frailty at wave 5, but the path was not significant between waves 5 and 7 (probit regression coefficient 0.05; 95% CI, -0.02 to 0.13). The paths from frailty to edentulousness were not significant at either time point (probit regression coefficients 0.09 [95% CI, -0.10 to 0.279] and 0.14 [95% CI, -0.03 to 0.31] for waves 3-5 and waves 5-7, respectively). The estimates of indirect paths via loneliness and CRP were of small magnitude but significant at both time points. No significant mediation was observed via the consumption of fruit and vegetables. Health promotion strategies aimed at preserving natural teeth and tackling loneliness in older people may have the potential to prevent frailty.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"34 1","pages":"220345251414409"},"PeriodicalIF":7.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374026","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}
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