Su Young Ki, Jea Hwa Jang, Dong-Hoon Kim, Yong Taek Jeong
{"title":"c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury","authors":"Su Young Ki, Jea Hwa Jang, Dong-Hoon Kim, Yong Taek Jeong","doi":"10.1038/s41368-025-00387-3","DOIUrl":"https://doi.org/10.1038/s41368-025-00387-3","url":null,"abstract":"<p>Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function. While denervation-induced taste bud degeneration and subsequent regeneration were discovered decades ago, the mechanisms underlying these phenomena (e.g., heterogenous cellular responses to nerve injury and the signaling pathways involved) remain poorly understood. Here, using mouse genetics, nerve injury models, pharmacologic manipulation, and taste bud organoid models, we identify a specific subpopulation of taste cells, predominantly c-Kit-expressing sweet cells, that exhibit superior resistance to nerve injury. We found the c-Kit inhibitor imatinib selectively reduced the number of residual c-Kit-expressing sweet cells at post-operation week 2, subsequently attenuating the re-emergence of other type II cells by post-operation week 4. In taste bud organoids, c-Kit-expressing cells were resistant to R-spondin withdrawal but susceptible to imatinib, while other taste cell types showed the opposite behavior. We also observed a distinct population of residual taste cells that acquired stem-like properties, generating clonal descendent cells among suprabasal keratinocytes independent of c-Kit signaling. Together, our findings reveal that c-Kit signaling confers resilience on c-Kit-expressing sweet cells and supports the broader reconstruction of taste buds during the later regenerative stage following nerve injury.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"23 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719395","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}
Jianing Liu, Junxi He, Ziqi Zhang, Lu Liu, Yuan Cao, Xiaohui Zhang, Xinyue Cai, Xinyan Luo, Xiao Lei, Nan Zhang, Hao Wang, Ji Chen, Peisheng Liu, Jiongyi Tian, Jiexi Liu, Yuru Gao, Haokun Xu, Chao Ma, Shengfeng Bai, Yubohan Zhang, Yan Jin, Chenxi Zheng, Bingdong Sui, Fang Jin
{"title":"Single-cell transcriptomics identifies PDGFRA+ progenitors orchestrating angiogenesis and periodontal tissue regeneration","authors":"Jianing Liu, Junxi He, Ziqi Zhang, Lu Liu, Yuan Cao, Xiaohui Zhang, Xinyue Cai, Xinyan Luo, Xiao Lei, Nan Zhang, Hao Wang, Ji Chen, Peisheng Liu, Jiongyi Tian, Jiexi Liu, Yuru Gao, Haokun Xu, Chao Ma, Shengfeng Bai, Yubohan Zhang, Yan Jin, Chenxi Zheng, Bingdong Sui, Fang Jin","doi":"10.1038/s41368-025-00384-6","DOIUrl":"https://doi.org/10.1038/s41368-025-00384-6","url":null,"abstract":"<p>Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA<sup>+</sup> dental follicle stem cells (DFSCs) and CD31<sup>+</sup> Endomucin<sup>+</sup> endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA<sup>+</sup> DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA<sup>+</sup> DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"17 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694228","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}
Preethi Balan, Junfeng Zhang, Kok Hian Tan, Upul Cooray, Ryan WK Lee, Mah Lay Ong, Chaminda Jaya Seneviratne
{"title":"Saliva as a non-invasive matrix for assessing xenobiotic metabolites and metabolomes: implications for maternal health and preeclampsia","authors":"Preethi Balan, Junfeng Zhang, Kok Hian Tan, Upul Cooray, Ryan WK Lee, Mah Lay Ong, Chaminda Jaya Seneviratne","doi":"10.1038/s41368-025-00390-8","DOIUrl":"https://doi.org/10.1038/s41368-025-00390-8","url":null,"abstract":"<p>Chemical exposure during prenatal development has significant implications for both maternal and child health. Compared to blood, saliva is a non-invasive and less resource-intensive, alternative. Given the temporal variability of xenobiotic metabolites (XM), repeated sampling is essential. Therefore, saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes. Despite its potential, no studies have explored saliva for XM measurement. This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women. Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24–34 weeks gestation. Metabolomes and exposomes were annotated using the Human Metabolome and U.S. Environmental Protection Agency databases. Metabolome-XM associations were clustered using Glay community clustering. Linear regression models, adjusted for age, estimated associations between catecholamines and XMs. XM levels were validated in a cohort of women (<i>n</i> = 14) with and without preeclampsia. Our study identified 582 metabolomes and 125 XM in saliva, demonstrating its potential as a matrix for exposure measurement. After false discovery rate correction, 18 109 significant metabolome-XM associations were identified. Community clustering revealed 37 connected clusters, with the largest cluster (238 nodes) enriched in tyrosine and catecholamine metabolism. Food-contact-chemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels. Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls. This study demonstrates that saliva contains valuable molecular data for measuring exposomes. Food-related chemicals were associated with higher catecholamine levels, which may be relevant to the prevalence of hypertensive crises in pregnancy.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"14 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677543","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}
Juan Xia, Xiaoan Tao, Qinchao Hu, Wei Luo, Xiuzhen Tong, Gang Zhou, Hongmei Zhou, Hong Hua, Guoyao Tang, Tong Wu, Qianming Chen, Yuan Fan, Xiaobing Guan, Hongwei Liu, Chaosu Hu, Yongmei Zhou, Xuemin Shen, Lan Wu, Xin Zeng, Qing Liu, Renchuan Tao, Yuan He, Yang Cai, Wenmei Wang, Ying Zhang, Yingfang Wu, Minhai Nie, Xin Jin, Xiufeng Wei, Yongzhan Nie, Changqing Yuan, Bin Cheng
{"title":"Expert consensus on the prevention and treatment of radiochemotherapy-induced oral mucositis","authors":"Juan Xia, Xiaoan Tao, Qinchao Hu, Wei Luo, Xiuzhen Tong, Gang Zhou, Hongmei Zhou, Hong Hua, Guoyao Tang, Tong Wu, Qianming Chen, Yuan Fan, Xiaobing Guan, Hongwei Liu, Chaosu Hu, Yongmei Zhou, Xuemin Shen, Lan Wu, Xin Zeng, Qing Liu, Renchuan Tao, Yuan He, Yang Cai, Wenmei Wang, Ying Zhang, Yingfang Wu, Minhai Nie, Xin Jin, Xiufeng Wei, Yongzhan Nie, Changqing Yuan, Bin Cheng","doi":"10.1038/s41368-025-00382-8","DOIUrl":"https://doi.org/10.1038/s41368-025-00382-8","url":null,"abstract":"<p>Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"23 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629720","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":"Expert consensus on peri-implant keratinized mucosa augmentation at second-stage surgery","authors":"Shiwen Zhang, Rui Sheng, Zhen Fan, Fang Wang, Ping Di, Junyu Shi, Duohong Zou, Dehua Li, Yufeng Zhang, Zhuofan Chen, Guoli Yang, Wei Geng, Lin Wang, Jian Zhang, Yuanding Huang, Baohong Zhao, Chunbo Tang, Dong Wu, Shulan Xu, Cheng Yang, Yongbin Mou, Jiacai He, Xingmei Yang, Zhen Tan, Xiaoxiao Cai, Jiang Chen, Hongchang Lai, Zuolin Wang, Quan Yuan","doi":"10.1038/s41368-025-00379-3","DOIUrl":"https://doi.org/10.1038/s41368-025-00379-3","url":null,"abstract":"<p>Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"19 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319323","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}
Paras Ahmad, Nathan Estrin, Nima Farshidfar, Yufeng Zhang, Richard J. Miron
{"title":"Isolation methods of exosomes derived from dental stem cells","authors":"Paras Ahmad, Nathan Estrin, Nima Farshidfar, Yufeng Zhang, Richard J. Miron","doi":"10.1038/s41368-025-00370-y","DOIUrl":"https://doi.org/10.1038/s41368-025-00370-y","url":null,"abstract":"<p>Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities. Recently, mesenchymal stem cells have been redefined as “medical signaling cells,” with their primary biological effects mediated through exosome secretion. These exosomes, which contain lipids, proteins, RNA, and metabolites, are crucial in regulating various biological processes and enhancing regenerative therapies. Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects, low immunogenicity, excellent biocompatibility, and high drug-loading capacity. Dental stem cells, including those from apical papilla, gingiva, dental pulp, and other sources, are key contributors to exosome-mediated regenerative effects, such as tumor cell apoptosis, neuroprotection, angiogenesis, osteogenesis, and immune modulation. Despite their promise, clinical application of exosomes is limited by challenges in isolation techniques. Current methods face issues of complexity, inefficiency, and insufficient purity, hindering detailed analysis. Recent advancements, such as micro-electromechanical systems, alternating current electroosmosis, and serum-free three-dimensional cell cultures, have improved exosome isolation efficacy. This review synthesizes nearly 200 studies on dental stem cell-derived exosomes, highlighting their potential in treating a wide range of conditions, including periodontal diseases, cancer, neurodegenerative disorders, diabetes, and more. Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"12 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296120","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":"Platelet methyltransferase-like protein 4-mediated mitochondrial DNA metabolic disorder exacerbates oral mucosal immunopathology in hypoxia","authors":"Yina Zhu, Meichen Wan, Yutong Fu, Junting Gu, Zhaoyang Ren, Yun Wang, Kehui Xu, Jing Li, Manjiang Xie, Kai Jiao, Franklin Tay, Lina Niu","doi":"10.1038/s41368-025-00373-9","DOIUrl":"https://doi.org/10.1038/s41368-025-00373-9","url":null,"abstract":"<p>Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N<sup>6</sup>-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"5 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269144","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}
Puting Dong, Mengdi Yang, Jie Hu, Lujia Cen, Peng Zhou, Difei Xu, Peng Xiong, Jiahe Li, Xuesong He
{"title":"Identification of a Fusobacterial RNA-binding protein involved in host small RNA-mediated growth inhibition","authors":"Puting Dong, Mengdi Yang, Jie Hu, Lujia Cen, Peng Zhou, Difei Xu, Peng Xiong, Jiahe Li, Xuesong He","doi":"10.1038/s41368-025-00378-4","DOIUrl":"https://doi.org/10.1038/s41368-025-00378-4","url":null,"abstract":"<p>Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in <i>Fusobacterium nucleatum</i> (<i>Fn</i>), which binds <i>Fn</i>-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the <i>Fn</i> type strain and a clinical tumor isolate, deletion of <i>ptaT</i> led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between <i>Fn</i> wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and <i>Fn</i>-targeting tsRNA. By uncovering the first RNA-binding protein in <i>Fn</i> implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"217 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260489","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}