International Journal of Oral Science最新文献_第7页

Wnt3a promotes in situ dentin formation through NKD1-MSX1 axis-mediated odontogenic differentiation of dental pulp stem cells. Wnt3a通过NKD1-MSX1轴介导的牙髓干细胞成牙分化促进原位牙本质形成。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-01-13 DOI: 10.1038/s41368-025-00406-3

Haoran Du,Qiong Li,Chenchen Zhou,Junji Xu,Kang Gao,Zixiao Li,Yifan Xu,Ousheng Liu,Bing Li,Jianguang Xu,Jingsong Wang,Hideaki Kagami,Xianqi Li,Su Chen,Jian Zhou

{"title":"Wnt3a promotes in situ dentin formation through NKD1-MSX1 axis-mediated odontogenic differentiation of dental pulp stem cells.","authors":"Haoran Du,Qiong Li,Chenchen Zhou,Junji Xu,Kang Gao,Zixiao Li,Yifan Xu,Ousheng Liu,Bing Li,Jianguang Xu,Jingsong Wang,Hideaki Kagami,Xianqi Li,Su Chen,Jian Zhou","doi":"10.1038/s41368-025-00406-3","DOIUrl":"https://doi.org/10.1038/s41368-025-00406-3","url":null,"abstract":"The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation, yet the molecular mechanisms governing odontoblast differentiation remain poorly understood. In the current study, we revealed a distinct NKD1+ subpopulation exhibiting secretory odontoblast characteristics, which was specifically induced in dental pulp stem cells (DPSCs) by Wnt3a, but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling. We then found that the NKD1+ subpopulation was functional conservation, which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models, as well as within the apical open area in human molars. This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1+ cells were active dentin-secreting odontoblasts. Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1+ lineage. Mechanistically, Wnt3a orchestrates a tripartite cascade: upregulating NKD1/MSX1 expression, triggering NKD1 membrane detachment, and facilitating direct NKD1-MSX1 interaction to promote MSX1 nuclear translocation. CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulators, establishing its necessity for odontogenic gene activation. Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation. This study delineates an evolutionarily conserved Wnt3a-NKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment, providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"250 1","pages":"9"},"PeriodicalIF":14.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956063","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}

引用次数: 0

MARCH2 suppresses odontoblast differentiation by polyubiquitinating PTPRD. MARCH2通过泛素化PTPRD抑制成牙细胞分化。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-01-10 DOI: 10.1038/s41368-025-00407-2

Hao Feng,Jiaxin Niu,Zhi Chen,Guobin Yang,Guohua Yuan

{"title":"MARCH2 suppresses odontoblast differentiation by polyubiquitinating PTPRD.","authors":"Hao Feng,Jiaxin Niu,Zhi Chen,Guobin Yang,Guohua Yuan","doi":"10.1038/s41368-025-00407-2","DOIUrl":"https://doi.org/10.1038/s41368-025-00407-2","url":null,"abstract":"Dentin, the main component of dental hard tissues, is produced by differentiated odontoblasts. How odontoblast differentiation is regulated remains understudied. Here, we screen that the expression of membrane-associated RING finger protein 2 (March2) is the highest among all March family members, with an increasing trend during odontoblast differentiation. In mouse incisors and molars, MARCH2 is moderately expressed in the undifferentiated dental papilla cells and strongly expressed in the odontoblasts. Knockdown and overexpression experiments demonstrate that MARCH2 inhibits odontoblastic differentiation of mouse dental papilla cells (mDPCs). Additionally, both March2 deficient mice and mice with odontoblast specific knockdown of March2 exhibit the phenotype of increased dentin thickness, accelerated dentin deposition as well as elevated expression levels of odontoblast markers compared with control littermates. Therefore, MARCH2 plays an inhibitory role in odontoblast differentiation. Mechanistically, MARCH2 interacts with protein tyrosine phosphatase receptor delta (PTPRD) and facilitates its K27-linked polyubiquitination and subsequent degradation, which is dependent on the ligase activity of MARCH2. The presence of MARCH2 promotes the translocation of PTPRD from the cell membrane to the lysosome, thereby enhancing its degradation via the lysosomal pathway. Further experiments show that knockdown of endogenous Ptprd impairs odontoblastic differentiation of mDPCs. Ptprd and March2 double knockdown in mDPCs apparently reversed the enhanced odontoblastic differentiation by knockdown of March2 alone, indicating that MARCH2 inhibits odontoblastic differentiation by promoting PTPRD degradation. This study unveils a novel mechanism where an E3 ubiquitin ligase regulates odontoblast differentiation through post-translational modification of a membrane protein, highlighting a promising direction for future exploration.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"140 1","pages":"5"},"PeriodicalIF":14.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937883","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}

引用次数: 0

Periodontitis pathogen Porphyromonas gingivalis promotes chronic obstructive pulmonary disease via affecting neutrophils chemotaxis and function. 牙周炎病原体牙龈卟啉单胞菌通过影响中性粒细胞趋化性和功能促进慢性阻塞性肺疾病。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-01-09 DOI: 10.1038/s41368-025-00397-1

Luyao Zhang, Huan Tian, Yuanyuan Ma, Jing Xu, Chang Guo, Zuomin Wang, Jie Ma

{"title":"Periodontitis pathogen Porphyromonas gingivalis promotes chronic obstructive pulmonary disease via affecting neutrophils chemotaxis and function.","authors":"Luyao Zhang, Huan Tian, Yuanyuan Ma, Jing Xu, Chang Guo, Zuomin Wang, Jie Ma","doi":"10.1038/s41368-025-00397-1","DOIUrl":"10.1038/s41368-025-00397-1","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD), a disease responsible for early mortality worldwide, is well accepted to be associated with periodontitis epidemiologically. Although both of the diseases are the multi-microbial inflammatory disease, the precise underlying mechanisms by which periodontitis influences the progression of COPD remains largely unknown. Here, we established COPD accompanied with periodontitis mouse models and observed the pronounced progress in pulmonary symptoms and histopathology, characterized by poorer respiratory function, thickened bronchial walls, and increased neutrophils infiltration in lung tissue. Mechanistically, periodontitis pathogen Porphyromonas gingivalis (P. gingivalis) relocated in the lung through the respiratory tract and LPS from P. gingivalis promoted the secretion of chemokines CXCL2 and G-CSF of alveolar epithelial cells through NF-κB and p38 MAPK pathways to recruit neutrophils. Furthermore, exposure to P. gingivalis of infiltrated neutrophils released matrix metallopeptidase-8 (MMP-8) and neutrophil elastase (NE), which aggravated airway inflammation and tissue damage. These findings indicated that periodontitis could exacerbate COPD via its pathogen P. gingivalis, which translocated in the lung and stimulated neutrophil chemotaxis and activation in the lung.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":"4"},"PeriodicalIF":17.6,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SMAD7 regulates the canonical Wnt signaling through TGF-β cascade crosstalk and SMAD7/β-CATENIN transcription factor complex formation during tooth regeneration. SMAD7在牙齿再生过程中通过TGF-β级联串和SMAD7/β-CATENIN转录因子复合物的形成调控典型Wnt信号。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-01-06 DOI: 10.1038/s41368-025-00393-5

Qiuyu Chen,Zhi Liu,Bohuai Zhou,Cheng Liang,Yiping Chen,Weidong Tian,Tian Chen

{"title":"SMAD7 regulates the canonical Wnt signaling through TGF-β cascade crosstalk and SMAD7/β-CATENIN transcription factor complex formation during tooth regeneration.","authors":"Qiuyu Chen,Zhi Liu,Bohuai Zhou,Cheng Liang,Yiping Chen,Weidong Tian,Tian Chen","doi":"10.1038/s41368-025-00393-5","DOIUrl":"https://doi.org/10.1038/s41368-025-00393-5","url":null,"abstract":"Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation, apoptosis, and differentiation, with the Wnt/β-catenin signaling pathway playing a pivotal role. However, the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear. Smad7, a key antagonist of the TGF-β superfamily, is essential for maintaining tissue homeostasis and ensuring proper cellular function. Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells, resulting in small molars. Here, we identified SMAD7 expression in human dental papilla and dental pulp, colocalized with β-CATENIN and cell proliferation-related proteins. RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs. Using lentivirus transfection, we established SMAD7-knockdown human dental papilla stem cells, which manifested remarkably blunt proliferation rate, along with diminished Wnt signaling activity. In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation. Mechanistically, we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays. Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities, indicating both direct and indirect regulatory mechanisms. These findings highlight the critical role of SMAD7 in the proliferation and differentiation of human dental stem cells, which could contribute to dental tissue regeneration and engineering.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"84 1","pages":"2"},"PeriodicalIF":14.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903709","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}

引用次数: 0

Structure insight into FtsZ function maintaining under acid stress of Streptococcus mutans. 变形链球菌酸胁迫下FtsZ功能维持的结构研究。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-01-04 DOI: 10.1038/s41368-025-00400-9

Yuxing Chen,Yongliang Li,Jiahao Niu,Liuchang Yang,Yaqi Chi,Xue Cai,Fengjiao Xin,Jie Zhang,Xianyang Fang,Yiqin Gao,Manas Mondal,Xiaoyan Wang

{"title":"Structure insight into FtsZ function maintaining under acid stress of Streptococcus mutans.","authors":"Yuxing Chen,Yongliang Li,Jiahao Niu,Liuchang Yang,Yaqi Chi,Xue Cai,Fengjiao Xin,Jie Zhang,Xianyang Fang,Yiqin Gao,Manas Mondal,Xiaoyan Wang","doi":"10.1038/s41368-025-00400-9","DOIUrl":"https://doi.org/10.1038/s41368-025-00400-9","url":null,"abstract":"Understanding the acid resistance mechanism of S. mutans is crucial for preventing dental caries. FtsZ is the core protein for cell division in bacteria that can polymerize into Z-rings and drive cytokinesis. Our previous study revealed that the FtsZ in S. mutans (SmFtsZ) has higher self-assembly and GTPase activity under acidic stress, which may be responsible for acid resistance and cariogenesis of S. mutans. However, the functional structure mechanism of SmFtsZ under low pH conditions is still unclear. Here, we further reported the crystal structure of S. mutans FtsZ, revealing a unique lateral interface. Through protein polymerization and GTPase activity assay, we experimentally demonstrated that the mutation of Arg68 on this lateral interface significantly reduced the functional activity of FtsZ in an acidic environment. The phenotype assay and rat caries model further showed that the mutation of Arg68 effectively inhibited the acid resistance of S. mutans and the occurrence and progress of dental caries in vivo. By employing a molecular dynamics simulation analysis, we conclude that the mutation of Arg68 disrupts the conformation change necessary for SmFtsZ polymerization under acidic conditions. Our study proposes a novel mechanism to maintain FtsZ function in bacteria and could be a potential target for antimicrobial drugs to inhibit the growth of S. mutans in acidic environments.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"26 1","pages":"3"},"PeriodicalIF":14.9,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893972","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}

引用次数: 0

Next-generation craniomaxillofacial implants for reconstructive surgery: balancing biomechanics, biocompatibility, and bioactivity. 用于重建手术的下一代颅颌面植入物：平衡生物力学、生物相容性和生物活性。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-01-04 DOI: 10.1038/s41368-025-00410-7

Bozhi Hou,Yuehua Li,Raymond Chung Wen Wong

{"title":"Next-generation craniomaxillofacial implants for reconstructive surgery: balancing biomechanics, biocompatibility, and bioactivity.","authors":"Bozhi Hou,Yuehua Li,Raymond Chung Wen Wong","doi":"10.1038/s41368-025-00410-7","DOIUrl":"https://doi.org/10.1038/s41368-025-00410-7","url":null,"abstract":"Next-generation craniomaxillofacial implants (CMFIs) are redefining personalized bone reconstruction by balancing and optimizing biomechanics, biocompatibility, and bioactivity-the \"3Bs\". This review highlights recent progress in implant design, material development, additive manufacturing, and preclinical evaluation. Emerging biomaterials, including bioresorbable polymers, magnesium alloys, and composites with bioactive ceramics, enable patient-specific solutions with improved safety and functionality. Triply periodic minimal surface (TPMS) architectures exemplify how structural design can enhance both mechanical performance and biological integration. Additive manufacturing technologies further allow the fabrication of geometrically complex, customized implants that meet individual anatomical and pathological needs. In parallel, multiscale evaluation techniques-from mechanical testing to in vitro and in vivo models-provide comprehensive insights into implant performance and safety. Looking ahead, the field is poised to benefit from several transformative trends: the development of smart and multifunctional biomaterials; AI-driven design frameworks that leverage patient-specific data and computational modeling; predictive additive manufacturing with real-time quality control; and advanced biological testing platforms for preclinical evaluation. Together, these advances form the foundation of a data-informed, translational pipeline from bench to bedside. Realizing the full potential of next-generation CMFIs will require close interdisciplinary collaboration across materials science, computational engineering, and clinical medicine.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"34 1","pages":"1"},"PeriodicalIF":14.9,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893973","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}

引用次数: 0

Progressive tooth pattern changes in Cilk1-deficient mice depending on Hedgehog signaling. cilk1缺陷小鼠的渐进式牙齿模式改变依赖于Hedgehog信号。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2025-12-01 DOI: 10.1038/s41368-025-00405-4

Minjae Kyeong,Ju-Kyung Jeong,Dinuka Adasooriya,Shiqi Kan,Jiwoo Kim,Jieun Song,Sihyeon Park,Suyeon Je,Seok Jun Moon,Young-Bum Park,Hyuk Wan Ko,Eui-Sic Cho,Sung-Won Cho

{"title":"Progressive tooth pattern changes in Cilk1-deficient mice depending on Hedgehog signaling.","authors":"Minjae Kyeong,Ju-Kyung Jeong,Dinuka Adasooriya,Shiqi Kan,Jiwoo Kim,Jieun Song,Sihyeon Park,Suyeon Je,Seok Jun Moon,Young-Bum Park,Hyuk Wan Ko,Eui-Sic Cho,Sung-Won Cho","doi":"10.1038/s41368-025-00405-4","DOIUrl":"https://doi.org/10.1038/s41368-025-00405-4","url":null,"abstract":"Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1-/-;PCS1-MRCS1△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"1 1","pages":"71"},"PeriodicalIF":14.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644997","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}

引用次数: 0

Arginine modulates the pH, microbial composition, and matrix architecture of biofilms from caries-active patients. 精氨酸可调节龋活动性患者生物膜的pH值、微生物组成和基质结构。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2025-11-20 DOI: 10.1038/s41368-025-00404-5

Yumi C Del Rey,Pernille D Rikvold,Marie B Lund,Eero J Raittio,Andreas Schramm,Rikke L Meyer,Sebastian Schlafer

{"title":"Arginine modulates the pH, microbial composition, and matrix architecture of biofilms from caries-active patients.","authors":"Yumi C Del Rey,Pernille D Rikvold,Marie B Lund,Eero J Raittio,Andreas Schramm,Rikke L Meyer,Sebastian Schlafer","doi":"10.1038/s41368-025-00404-5","DOIUrl":"https://doi.org/10.1038/s41368-025-00404-5","url":null,"abstract":"The caries-preventive effects of arginine have been attributed to its impact on biofilm composition and pH. Recent in vitro studies suggest that arginine also affects the production of biofilm matrix components that contribute to virulence, but this mechanism has not been investigated clinically. This randomized, placebo-controlled, triple-blind, split-mouth in situ trial assessed arginine's impact on the microbial composition, matrix architecture, and microscale pH of biofilms from caries-active patients (N = 10). We also examined whether individual differences in the pH response to arginine were related to biofilm composition and matrix structure. Biofilms were grown for four days on carriers attached to intraoral splints. Three times daily, the biofilms were treated extraorally with sucrose (5 min), followed by arginine or placebo (30 min), in a split-mouth design. After growth, the microscale biofilm pH response to sucrose was monitored by pH ratiometry. Microbial biofilm composition and carbohydrate matrix architecture were analyzed by 16S rRNA gene sequencing and fluorescence lectin-binding analysis, respectively. Arginine treatment significantly mitigated sucrose-induced pH drops, reduced total carbohydrate matrix production, and altered the spatial distribution of fucose- and galactose-containing carbohydrates. Both arginine- and placebo-treated biofilms were dominated by streptococci and Veillonella spp. Paired analyses showed a significant reduction in mitis/oralis group streptococci and a non-significant increase in several arginine metabolizers in arginine-treated biofilms. Individual pH responses were not significantly associated with the abundance of specific bacterial taxa or carbohydrate matrix components. In conclusion, arginine reduced the virulence of biofilms from caries-active patients through multiple mechanisms, including suppressing matrix carbohydrate production.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"160 1","pages":"70"},"PeriodicalIF":14.9,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554741","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}

引用次数: 0

Porphyromonas gingivalis-induced glucose intolerance during periapical lesions requires its LPS throught a Th17 immune response. 牙龈卟啉单胞菌在根尖周围病变期间引起的葡萄糖耐受不良需要其LPS通过Th17免疫反应。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2025-11-13 DOI: 10.1038/s41368-025-00403-6

Sylvie Lê, Emma Sturaro, Charlotte Thomas, Thibault Canceill, Bertrand Ekambi, Nawel Fellouah, Claude Knauf, Anne Abot, Christophe Tenailleau, Benjamin Duployer, Pascale Loubieres, Alison Prosper, Swann Diemer, Rémy Burcelin, Franck Diemer, Matthieu Minty, Vincent Blasco-Baque

{"title":"Porphyromonas gingivalis-induced glucose intolerance during periapical lesions requires its LPS throught a Th17 immune response.","authors":"Sylvie Lê, Emma Sturaro, Charlotte Thomas, Thibault Canceill, Bertrand Ekambi, Nawel Fellouah, Claude Knauf, Anne Abot, Christophe Tenailleau, Benjamin Duployer, Pascale Loubieres, Alison Prosper, Swann Diemer, Rémy Burcelin, Franck Diemer, Matthieu Minty, Vincent Blasco-Baque","doi":"10.1038/s41368-025-00403-6","DOIUrl":"10.1038/s41368-025-00403-6","url":null,"abstract":"This study investigates the role of Interleukin 17 (IL-17) in exacerbating periapical lesions caused by Porphyromonas gingivalis (Pg) lipopolysaccharides (LPS) in the context of metabolic disease and its potential impact on glucose tolerance. Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions. After 1 month, they were fed a high-fat diet (HFD) for 2 months to simulate metabolic disease and oral microbiota dysbiosis. To explore the role of LPS from Pg, wild-type (WT) mice were challenged with purified LPS from Porphyromonas gingivalis, as well as with LPS-depleted and non-depleted Pg bacteria; IL-17 knockout (KO) mice were also included to assess the role of IL-17 signaling. The impact on bone lysis, periapical injury, glucose intolerance, and immune response was assessed. Results showed that in WT mice, the presence of LPS significantly worsened bone lysis, Th17 cell recruitment, and periapical injury. IL-17 KO mice exhibited reduced bone loss, glucose intolerance, and immune cell infiltration. Additionally, inflammatory markers in adipose tissue were lower in IL-17 KO mice, despite increased dysbiosis. The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances. Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes (T2D) risk in individuals with periapical disease.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"17 1","pages":"69"},"PeriodicalIF":17.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12615820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thymosin α1 alleviates pulpitis by inhibiting ferroptosis of dental pulp cells. 胸腺素α1通过抑制牙髓细胞铁下垂减轻牙髓炎。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2025-10-14 DOI: 10.1038/s41368-025-00394-4

Jie Wu,Qimei Gong,Wenxuan Liu,Aijia Chen,Zekai Liao,Yihua Huang,Wenkai Jiang,Zhongchun Tong

{"title":"Thymosin α1 alleviates pulpitis by inhibiting ferroptosis of dental pulp cells.","authors":"Jie Wu,Qimei Gong,Wenxuan Liu,Aijia Chen,Zekai Liao,Yihua Huang,Wenkai Jiang,Zhongchun Tong","doi":"10.1038/s41368-025-00394-4","DOIUrl":"https://doi.org/10.1038/s41368-025-00394-4","url":null,"abstract":"Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe2+ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe2+ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"23 1","pages":"68"},"PeriodicalIF":14.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288609","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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