International Journal of Oral Science最新文献_第2页

Gli2 and Gli3 synergistically mediate HH-TGF-β crosstalk in mesenchymal progenitor cells to orchestrate tooth root morphogenesis. Gli2和Gli3协同介导间充质祖细胞中HH-TGF-β串音，协调牙根形态发生。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-03-12 DOI: 10.1038/s41368-026-00427-6

Tao Zhou,Linyang Huang,Yaxin Xie,Yijia Yin,Yufei Yao,Li Mei,Paul R Cooper,Hu Zhao,Xianglong Han,Junjun Jing

{"title":"Gli2 and Gli3 synergistically mediate HH-TGF-β crosstalk in mesenchymal progenitor cells to orchestrate tooth root morphogenesis.","authors":"Tao Zhou,Linyang Huang,Yaxin Xie,Yijia Yin,Yufei Yao,Li Mei,Paul R Cooper,Hu Zhao,Xianglong Han,Junjun Jing","doi":"10.1038/s41368-026-00427-6","DOIUrl":"https://doi.org/10.1038/s41368-026-00427-6","url":null,"abstract":"Hedgehog (HH) signaling is essential in directing the fate determination of postmigratory cranial neural crest cells (CNCCs) to ensure proper craniofacial development. Gli transcription factors (TFs) are established as primary effectors of HH signaling, yet their distinct roles and regulatory mechanisms in governing cell commitment and differentiation of postmigratory CNCCs remain poorly understood. Here, using tooth root as a model, we combined transgenic mouse models with bioinformatic analyses to interrogate the functions of Gli2 and Gli3 in CNCC-derived root progenitor cells of the mouse molar. We revealed that loss of Gli3 alone in dental mesenchymal root progenitor cells caused shortened roots and that concurrent loss of Gli2 and Gli3 exacerbated root malformations, concomitant with profound impairments in cell proliferation and multilineage differentiation, suggesting a synergistic interaction between Gli2 and Gli3 during tooth root development. Mechanistically, Gli2 and Gli3 cooperatively regulated the transcription of Acvr2b, thereby modulating the activity of TGF-β/SMAD signaling within the dental mesenchyme. This Gli2/Gli3-TGF-β signaling cascade was critical for the lineage specification of tooth root progenitor cells during molar morphogenesis. Collectively, this work uncovers synergistic interactions of Gli2 and Gli3 in orchestrating tooth root morphogenesis and provides a novel insight into HH-TGF-β crosstalk in cell fate decisions of postmigratory CNCCs.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"26 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393988","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

Defining subcellular synovial responses in TMJ osteoarthritis onset via mechanical stress and articular disk derangement models. 通过机械应力和关节盘紊乱模型确定TMJ骨关节炎发病时的亚细胞滑膜反应。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-03-12 DOI: 10.1038/s41368-025-00411-6

Kazuhiro Shibusaka,Soichiro Negishi,Asuka Terashima,Miki Maemura,Hiroshi Yoshida,Masahiro Hosonuma,Nobuhiro Sakai,Young Kwan Kim,Yutaka Suzuki,Hiroyuki Okada,Fumiko Yano

{"title":"Defining subcellular synovial responses in TMJ osteoarthritis onset via mechanical stress and articular disk derangement models.","authors":"Kazuhiro Shibusaka,Soichiro Negishi,Asuka Terashima,Miki Maemura,Hiroshi Yoshida,Masahiro Hosonuma,Nobuhiro Sakai,Young Kwan Kim,Yutaka Suzuki,Hiroyuki Okada,Fumiko Yano","doi":"10.1038/s41368-025-00411-6","DOIUrl":"https://doi.org/10.1038/s41368-025-00411-6","url":null,"abstract":"Temporomandibular joint osteoarthritis (TMJ-OA), the most common degenerative disease of the TMJ, is influenced by various adaptive, inflammatory, and mechanical stressors. In this study, we describe molecular alterations of the synovium of the articular disk in response to mechanical and inflammatory stimuli. Using an integrated transcriptomic approach combining subcellular spatial transcriptomics and single-cell RNA sequencing in murine models of mechanical stress and articular disk derangement, we characterized synovial changes associated with adipogenesis, fibrosis, and macrophage activation. In addition, cell type-and cluster-specific catabolic changes were observed under these stress conditions, suggesting potential contributions to TMJ-OA onset. These results provide a methodology-oriented resource for investigating the molecular pathology of TMJ disorders and may help guide future studies toward the development of targeted therapeutic strategies.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393857","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

Bioengineered α-Hairpin peptide TKH with GKG linker: a LLPS-mediated biomimetic mineralization system for intrafibrillar remineralization and deep dentin tubule occlusion 带有GKG连接体的生物工程α-发夹肽TKH：用于纤维内再矿化和牙本质深部小管闭塞的llps介导的仿生矿化系统

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-03-05 DOI: 10.1038/s41368-026-00425-8

Yeling Ou, Jing Wang, Luoyao Wang, Haisheng Wang, Fengfan He, Longjiang Ding, Yanping Zhou, Sili Han, Linglin Zhang

{"title":"Bioengineered α-Hairpin peptide TKH with GKG linker: a LLPS-mediated biomimetic mineralization system for intrafibrillar remineralization and deep dentin tubule occlusion","authors":"Yeling Ou, Jing Wang, Luoyao Wang, Haisheng Wang, Fengfan He, Longjiang Ding, Yanping Zhou, Sili Han, Linglin Zhang","doi":"10.1038/s41368-026-00425-8","DOIUrl":"https://doi.org/10.1038/s41368-026-00425-8","url":null,"abstract":"Dentin hypersensitivity (DH) originates from collagen exposure and dentinal tubules (DTs) patency caused by mechanical abrasion or demineralization. For an effective long-term therapeutic desensitizing agent, the ability to achieve deep tubular occlusion, stable remineralization, and satisfactory biocompatibility simultaneously is essential. In this study, we designed a novel α-hairpin peptide, TKH, engineered by incorporating a flexible GKG linker into an α-helical template, and provide an analysis of its liquid–liquid phase separation (LLPS) and self-assembly properties. TKH effectively stabilized amorphous calcium phosphate and facilitated intrafibrillar mineralization within collagen fibrils. In vitro and in vivo remineralization studies combined with molecular dynamics (MD) simulations demonstrated that TKH promoted the peptide self-assembly through LLPS, hydroxyapatite (HA) adsorption, and amorphous calcium phosphate (ACP) stabilization, ultimately achieving intrafibrillar and extrafibrillar mineralization to seal DTs, alongside excellent biosafety. These findings highlight the potential of TKH as a promising peptide-based biomaterial for dentin remineralization and the treatment of dentin hypersensitivity.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"61 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346823","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

JAK-STAT signaling: molecular mechanism and targeted treatment in dento-maxillofacial abnormalities. JAK-STAT信号：牙颌面异常的分子机制及靶向治疗。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-03-05 DOI: 10.1038/s41368-025-00399-z

Zihan Huang,Yiwen Cui,Wenyi Zhang,Jiachen Shen,Qinggang Dai,Siyuan Sun,Lingyong Jiang

{"title":"JAK-STAT signaling: molecular mechanism and targeted treatment in dento-maxillofacial abnormalities.","authors":"Zihan Huang,Yiwen Cui,Wenyi Zhang,Jiachen Shen,Qinggang Dai,Siyuan Sun,Lingyong Jiang","doi":"10.1038/s41368-025-00399-z","DOIUrl":"https://doi.org/10.1038/s41368-025-00399-z","url":null,"abstract":"Dento-maxillofacial abnormalities are highly prevalent and arise as a result of a variety of etiological factors, presenting substantial challenges to treatment. The JAK-STAT signaling plays a pivotal role in dentofacial development, regulating endochondral ossification, intramembranous ossification, dental follicle formation, and enamel development. Mutations in the JAK-STAT signaling lead to syndromes associated with severe dento-maxillofacial abnormalities, including Growth Hormone Insensitivity Syndrome and Autosomal Dominant Hyper-IgE Syndrome. Corresponding mouse disease models have been developed to simulate the phenotypes observed in clinical patients and investigate their underlying mechanism. Meanwhile, several medications targeting JAK-STAT signaling, including baricitinib and imatinib, have been developed for clinical application, demonstrating significant effects in skeletal disorders such as osteoporosis and osteoarthritis, indicating promising effects in development and abnormalities of dento-maxillofacial. In this review, we aim to summarize the role of JAK-STAT signaling in the development and abnormalities of dento-maxillofacial bone, and the relevant molecules that may be utilized for clinical treatment, to shed new light on the precise treatment of dento-maxillofacial abnormalities.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"53 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350369","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

Correction: Antisense oligonucleotide targeting TARDBP-EGFR splicing axis inhibits progression of oral squamous cell carcinoma through ABCA1-regulated cholesterol efflux. 纠正：靶向TARDBP-EGFR剪接轴的反义寡核苷酸通过abca1调节的胆固醇外排抑制口腔鳞状细胞癌的进展。

IF 12.2 1区医学

International Journal of Oral Science Pub Date : 2026-03-04 DOI: 10.1038/s41368-026-00434-7

Nan Ni, Moxu Wang, Zhiran Yuan, Leqi Zhang, Jilin Cai, Qingqing Du, Pengcheng Li, Chang Gao, Hanwen Zhang, Yuancheng Li, Hua Yuan

引用次数: 0

KDM6B/Pdk1 glycolytic pathway-driven ZEB2 lactylation promotes cellular cementum formation. KDM6B/Pdk1糖酵解途径驱动的ZEB2乳酸化促进细胞骨质形成。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-03-03 DOI: 10.1038/s41368-025-00420-5

Zhengkun Yang,Huiyi Wang,Junhong Xiao,Qiudong Yang,Jiahui Sun,Heyu Liu,Zhendong Huang,Li Ma,Xin Huang,Chuan Wang,Xiaoxuan Wang,Zhengguo Cao

{"title":"KDM6B/Pdk1 glycolytic pathway-driven ZEB2 lactylation promotes cellular cementum formation.","authors":"Zhengkun Yang,Huiyi Wang,Junhong Xiao,Qiudong Yang,Jiahui Sun,Heyu Liu,Zhendong Huang,Li Ma,Xin Huang,Chuan Wang,Xiaoxuan Wang,Zhengguo Cao","doi":"10.1038/s41368-025-00420-5","DOIUrl":"https://doi.org/10.1038/s41368-025-00420-5","url":null,"abstract":"Periodontitis is a common chronic inflammatory disease that ultimately results in irreversible tooth loss. Cementum, a bone-like tissue surrounding tooth roots, deteriorates as periodontitis advances, ultimately causing tooth loss. Therefore, cementum regeneration is considered a key factor in periodontal regeneration. Given the shared gene expression patterns and characteristics between cementum and bone, strategies for cementum regeneration may inform approaches for bone regeneration. Cementoblasts are responsible for cementum formation. This study identified lysine demethylase 6B (KDM6B) as a positive regulatory molecule that promotes cementoblast mineralization and formation. The seahorse assay revealed that KDM6B regulates glycometabolic reprogramming during cementoblast mineralization. Chromatin Immunoprecipitation (ChIP) sequencing and bulk RNA sequencing revealed that pyruvate dehydrogenase kinase 1 (PDK1), a crucial enzyme in glycolysis, is a direct target of KDM6B. Activation of the KDM6B-Pdk1 axis enhanced lactate production, driving lactylation of zinc finger E-box binding homeobox 2 (ZEB2). ZEB2 lactylation subsequently promotes cementoblast mineralization. Moreover, both in vitro and in vivo experiments showed that sodium lactate supplementation restores mineralization impaired by KDM6B suppression. In conclusion, our findings identify the KDM6B-Pdk1-ZEB2 lactylation axis as essential for cementogenesis, providing new insights for periodontal regeneration strategies.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"69 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329191","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

Soluble Notch agonist enables human ameloblast maturation and enamel-like tissue formation for tooth regeneration. 可溶性Notch激动剂促进人成釉细胞成熟和牙釉质样组织形成，用于牙齿再生。

IF 12.2 1区医学

International Journal of Oral Science Pub Date : 2026-03-02 DOI: 10.1038/s41368-026-00429-4

Anjali P Patni, Rubul Mout, Ammar Alghadeer, Rachel H Moore, Samera Nademi, Brandon J Ausk, Philippe Huber, Riya Keshri, Mary Regier, Robert A Cornell, Ted Gross, Benjamin S Freedman, George Q Daley, David Baker, Julie Mathieu, Hannele Ruohola-Baker

{"title":"Soluble Notch agonist enables human ameloblast maturation and enamel-like tissue formation for tooth regeneration.","authors":"Anjali P Patni, Rubul Mout, Ammar Alghadeer, Rachel H Moore, Samera Nademi, Brandon J Ausk, Philippe Huber, Riya Keshri, Mary Regier, Robert A Cornell, Ted Gross, Benjamin S Freedman, George Q Daley, David Baker, Julie Mathieu, Hannele Ruohola-Baker","doi":"10.1038/s41368-026-00429-4","DOIUrl":"10.1038/s41368-026-00429-4","url":null,"abstract":"Enamel, the hardest mineralized material in the human body, protects the underlying living tissues, the dentin and pulp of the tooth. However, over 90% of adults have lost or damaged enamel and cannot regenerate the protective structure due to lack of enamel-producing cells, ameloblasts. iPSC-derived secretory Ameloblasts (isAM) have promise in future regenerative dentistry. Today, it is not known why iAM maturation requires intimate contact with the dentin-producing cell type, odontoblast. Here, we reveal that one of the critical signaling ligands emanating from odontoblasts for ameloblast maturation is Delta, the ligand for Notch receptor. We showed that our designed, soluble Notch agonist can induce iAM organoid maturation in an unprecedented manner, without interactions with odontoblast layer. Notably, soluble Notch agonist induces the iAM maturation to a novel, WDR72-positive mature secretory AM stage (ismAM) in our ameloblast organoid model. When transplanted under the kidney capsule of NOD-SCID mice, these ismAM organoids generated enamel-like calcified material, as confirmed by microCT analysis, marking the first demonstration that Notch-activated iAM organoids can form such tissue in vivo. This novel maturation procedure enabled us to analyze the specific requirements of DLX3 function in ameloblasts, independent of its known function in odontoblasts. We now show that DLX3, a gene associated with Amelogenesis Imperfecta, is required on a cell-autonomous manner in human ameloblasts for the expression of Enamelin, MMP20, and WDR72, a role not previously demonstrated in mouse models.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12950815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326123","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

Single-cell transcriptional atlas reveals distinct immune-chondrocyte crosstalk mechanisms in temporomandibular joint osteoarthritis induced by different types of occlusal disorder 单细胞转录图谱揭示了不同类型咬合障碍诱导的颞下颌关节骨性关节炎中不同的免疫-软骨细胞串扰机制

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-03-01 DOI: 10.1038/s41368-025-00424-1

Kang Wang, Yusi Li, Shuaixi Xiang, Ningyi Shao, Peiqi Wang, Xianrui Yang, Xianglong Han, Qingfeng Li, Hui Xu

{"title":"Single-cell transcriptional atlas reveals distinct immune-chondrocyte crosstalk mechanisms in temporomandibular joint osteoarthritis induced by different types of occlusal disorder","authors":"Kang Wang, Yusi Li, Shuaixi Xiang, Ningyi Shao, Peiqi Wang, Xianrui Yang, Xianglong Han, Qingfeng Li, Hui Xu","doi":"10.1038/s41368-025-00424-1","DOIUrl":"https://doi.org/10.1038/s41368-025-00424-1","url":null,"abstract":"Temporomandibular joint (TMJ) osteoarthritis (OA) is a progressive degenerative disease in which the intricate mechanisms of the condyle cartilage damage are yet to be disclosed. A detailed characterization of cellular composition and signal networks involved in the pathogenesis is in need. This study, for the first time, identified chondrocytes heterogeneity and subchondral immune microenvironments based on single-cell transcriptomes of the mouse mandibular condyle, and provided insights into the cellular and signaling basis of the homeostasis of the condyle and pathogenesis of TMJOA by healthy-to-diseased comparisons. The differentially expressed gene pattern distinguished 8 chondrocyte subsets and 9 immune cell types in the condyle. Close interactions were found between these cell populations, with enhanced communication between chondrocytes and immune cell subsets in the condyles subjected to anterior premature contact (APC) model or unilateral anterior crossbite (UAC) model. The single-cell transcriptomic changes suggested predominant roles of neutrophils in immune-chondrocyte interactions in these occlusal disorder models. Neutrophils-derived TNF-α signaling was inferred to be the most greatly enhanced information flow in the condyle of the APC model, while increased Thbs1-Sdc4 signaling in mediating neutrophils-to-chondrocytes interactions was indicated in the UAC-model condyle, with predominant BSP signaling. Interfering in these signaling by drug administration demonstrated therapeutic potential for the APC- or UAC-induced TMJOA.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"57 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147320014","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

ANKRD1 sustains a neurogenic BMSC niche and counters cognitive aging ANKRD1维持神经源性BMSC生态位并对抗认知衰老

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-03-01 DOI: 10.1038/s41368-026-00428-5

Zifei Wang, Xiaoyun Liu, Wenyu Zhen, Fei Xu, Rui Wang, Wenhu Fan, Wenhao Zhang, Yulong Zhang, Wansu Sun, Mingyue Wu, Jiacai He, Hao Gu, Hengguo Zhang

{"title":"ANKRD1 sustains a neurogenic BMSC niche and counters cognitive aging","authors":"Zifei Wang, Xiaoyun Liu, Wenyu Zhen, Fei Xu, Rui Wang, Wenhu Fan, Wenhao Zhang, Yulong Zhang, Wansu Sun, Mingyue Wu, Jiacai He, Hao Gu, Hengguo Zhang","doi":"10.1038/s41368-026-00428-5","DOIUrl":"https://doi.org/10.1038/s41368-026-00428-5","url":null,"abstract":"Craniomaxillofacial bone marrow mesenchymal stromal cells (BMSCs) retaining neural crest–derived neurogenic niche is driven by lineage memory and niche homeostasis. Elucidating how the neurogenic potential is maintained is critical for neurological health. Here, we explored a neural crest-like progenitor niche in BMSCs with high neurogenic and proliferative capacity by single-cell transcriptomics. In which, ANKRD1 is a pivotal regulator sustaining the neurogenic reservoir. Importantly, ANKRD1 expression in this niche declines with aging and lineage commitment, coinciding with its redistribution from a diffuse nucleoplasmic pattern to perinuclear enrichment along the nuclear lamina and loss of neural potential. Mechanistically, ANKRD1 preserves neurogenic capacity by directly binding super-enhancers of neural marker genes (SOX2, NESTIN) and maintaining open chromatin architecture. Critically, neuron-targeted ANKRD1 delivery rescues spatial memory deficits in aged mice. These findings establish ANKRD1 as a therapeutically tractable regulator that sustains neurogenic chromatin reservoirs to support neurocognitive resilience, opening avenues to counter cognitive aging.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"27 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147320015","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

Identification of GLDN⁺ odontogenic stem cells as crucial for human tooth development and regeneration. 鉴定GLDN+牙源性干细胞对人类牙齿发育和再生至关重要。

IF 12.2 1区医学

International Journal of Oral Science Pub Date : 2026-02-28 DOI: 10.1038/s41368-025-00419-y

Chengcheng Liao, Jinglun Liu, Maojiao Li, Bingqian Yang, Yejia Yu, Jian Yang, Xiaoxia Su, Shixing Ma, Hanchao Li, Jingyi Zhang, Weidong Tian, Li Liao

{"title":"Identification of GLDN+ odontogenic stem cells as crucial for human tooth development and regeneration.","authors":"Chengcheng Liao, Jinglun Liu, Maojiao Li, Bingqian Yang, Yejia Yu, Jian Yang, Xiaoxia Su, Shixing Ma, Hanchao Li, Jingyi Zhang, Weidong Tian, Li Liao","doi":"10.1038/s41368-025-00419-y","DOIUrl":"10.1038/s41368-025-00419-y","url":null,"abstract":"The dental papilla (DP) is essential for the development of dentin and pulp. The extensive cellular heterogeneity within the DP is a critical factor underlying the complex and precise formation of dental structures during odontogenesis. However, the critical cell types within human DP that play essential role in tooth development and regeneration remain largely uncharacterized. In this study, we analyzed the heterogeneity of human DP cells using single-cell sequencing and identified Gliomedin (GLDN)+ DP stem cells (DPSCs) were a group of progenitors at an early stage of tooth development and play a key role in the development of pulp and dentin. GLDN+ DPSCs strategically accumulate in human DP tissue near the interface of the newly formed dentin or pulp. Functional assays demonstrated that GLDN+ DPSCs exhibited enhanced self-renewal, migratory capacity, and odontogenic differentiation potential in vitro compared to GLDN- DPSCs. Moreover, GLDN+ DPSCs effectively induce the migration and tube formation of endothelial cells, which are essential for tooth development. The ectopic dental pulp regeneration model confirmed that GLDN+ DPSCs can regenerate a vascularized dental pulp structure with an odontoblast layer in vivo. Given their functional capabilities, this population of cells has been designated as GLDN+ odontogenic stem cells (OSCs). Mechanistically, GLDN is essential for maintaining the phenotype and function of GLDN+ OSCs through BMP5 signaling via autocrine and paracrine mechanisms. In conclusion, this study identifies a previously uncharacterized essential subpopulation of OSCs essential for dental pulp development and regeneration.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317100","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