International Journal of Oral Science最新文献

{"title":"Autonomous robotic execution of nonlinear toolpaths for geometry-matched osteotomy in tooth autotransplantation: an in vitro study","authors":"Chen Liu, Guangwei Chen, Libin Zhou, Jun Qiu, Dongmei Li, Yuchen Liu, Zhiwen Li, Shizhu Bai, Yimin Zhao","doi":"10.1038/s41368-026-00446-3","DOIUrl":"https://doi.org/10.1038/s41368-026-00446-3","url":null,"abstract":"Tooth autotransplantation requires recipient socket preparation that matches donor root morphology while preserving surrounding bone. We developed an autonomous multi-axis robotic system that executes nonlinear, surface-conforming milling trajectories to create a geometry-matched socket and compared it with a static tooth-supported guide in forty 3D-printed mandibular models representing single-rooted and double-rooted anatomies. Recipient sockets were planned by offsetting the donor root surface by 0.5 mm and eliminating insertion axis undercuts. The robot executed the planned milling path with a depth-stop Lindemann bur, whereas the guide workflow used guided pilot drilling followed by freehand refinement. Robot assistance reduced deep positional errors and improved agreement between planned and prepared socket geometry, with the most pronounced benefit in double-rooted models, while overall preparation time was comparable between approaches. These findings support further clinical validation to confirm that autonomous robotic, surface-conforming osteotomy can improve full-depth geometric fidelity and reduce unnecessary bone removal in technique-sensitive autotransplantation procedures.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"14 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355659","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 treatment of condylar hyperplasia and secondary dento-maxillofacial deformities.","authors":"Ruiye Bi, Bassam M Abotaleb, Xiaofeng Bai, Kun Cao, Gang Chen, Jie Cheng, Weihua Guo, Min Hu, Li Huang, Xuanping Huang, Hongbing Jiang, Lingyong Jiang, Xiaolei Jin, Feiwu Kang, Tangxin Li, Wenyang Li, Shuguang Liu, Yanpu Liu, Yanshan Liu, Li Lu, Yisen Shao, Bin Shi, Guodong Song, Yuxiong Su, Jian Sun, Zhenglong Tang, Lei Tian, Maimaitituxun Tuerdi, Qilong Wan, Xiaoxia Wang, Xuejiu Wang, Yong Wang, Guomin Wu, Zhijian Xie, Guangqi Yan, Xuewen Yang, Meng You, Fenghe Zhang, Shilei Zhang, Guangsen Zheng, Songsong Zhu, En Luo","doi":"10.1038/s41368-026-00442-7","DOIUrl":"10.1038/s41368-026-00442-7","url":null,"abstract":"<p><p>Condylar hyperplasia (CH), characterized by progressive facial deviation, occlusion disorders, and temporomandibular joint dysfunction, often requires combined temporomandibular joint (TMJ)-orthognathic interventions to reconstruct joint and occlusal functions as well as rebuilding harmonious facial expressions. Managing the dentomaxillofacial deformities secondary to CH involves hyperplastic condylar resection, orthognathic surgery, facial contour surgery and orthodontic treatment. Based on the activity of condylar hypertrophy, the severity of dentomaxillofacial deformity and malocclusion, an individualized treatment plan should be formulated to reconstruct joint functions, correct deformities and recover occlusal relationships. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for surgical treatment strategies for patients with different CH types, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13236974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163192","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}

{"title":"OCT4-driven PER1 activation promotes odontogenic differentiation in senescent SCAP spheres.","authors":"Changfang Li, Zibin Zhang, Zhuoxin Yang, Tingjie Liu, Xiaoning He, Bei Li, Wei Wang","doi":"10.1038/s41368-026-00444-5","DOIUrl":"10.1038/s41368-026-00444-5","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) hold significant promise for applications in regenerative medicine, yet their therapeutic potential is often limited by replicative senescence. Identifying effective strategies to reverse replicative senescence in MSCs and elucidating the underlying molecular mechanisms are essential steps in advancing their clinical use. Here, this study demonstrated that the pluripotency regulator octamer-binding transcription factor 4 (OCT4) promoted odontogenic differentiation by activating period circadian regulator 1 (PER1) in replicative senescent stem cells from apical papilla (SCAP) spheres. Specifically, OCT4 overexpression significantly alleviated cell cycle arrest, reduced senescence-associated β-galactosidase activity, and downregulated the expression of senescence-related markers, including CDKN2A/P16, CDKN1A/P21, and TP53/P53. Moreover, this approach markedly enhanced the proliferation and odontogenic differentiation potential of SCAP spheres in vitro and promoted the formation of regenerative pulp-like tissue in vivo. Mechanistically, we demonstrated that OCT4 transcriptionally activated PER1 through direct binding to its promoter, thereby restoring the odontogenic differentiation capacity of replicative senescent SCAP. Collectively, our findings establish the OCT4-PER1 axis as a critical regulatory pathway that counteracts replicative senescence in SCAP. These insights suggest new therapeutic strategies targeting senescence-associated signaling pathways to enhance MSC-based regenerative outcomes.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156427","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}

{"title":"Kdf1 missense mutation caused enamel defects by disrupting cell adhesion and Hippo-YAP signaling in dental epithelium.","authors":"Pei Li, Runling Zeng, Jingyan Xue, Yaling Song, Jie Wu, Binghui Zeng, Ling Lin, Dongsheng Yu, Wei Zhao","doi":"10.1038/s41368-026-00445-4","DOIUrl":"10.1038/s41368-026-00445-4","url":null,"abstract":"<p><p>Amelogenesis imperfecta is a hereditary enamel defect arising from dental epithelium dysfunction. Although keratinocyte differentiation factor 1 (KDF1) acts as an intracellular regulator in epithelial cells, the underlying disease mechanism of the patient-derived KDF1 missense mutation in amelogenesis remains unclear. Here, we show that a patient-derived KDF1 mutation (c.908 G > C, p.R303P) causes enamel defects by disrupting cell adhesion and Hippo-YAP signaling. Immunohistochemistry revealed strong KDF1 expression throughout dental epithelium development, particularly at the cell membrane. Kdf1 mutation knock-in heterozygotes and homozygotes displayed graded defective enamel with reduced thickness, inadequate mineralization and disorganized microstructure. This phenotype correlated with a gradual reduction in enamel matrix proteins and proteases across genotypes. Bulk RNA sequencing of ameloblasts suggested marked changes in adhesion-related genes and the Hippo-YAP pathway. We characterized cellular consequences of this variant using both LS8 and ALC cell lines, which appeared abnormalities including accelerated proliferation, undermined differentiation, weakened adhesion, and enhanced migration. In vivo and in vitro findings supported a model wherein the KDF1 mutation impaired intercellular and cell-matrix adhesion in ameloblasts. As a result, ameloblast differentiation was hampered through excessive nuclear yes-associated protein (YAP) accumulation and overactivation of downstream proliferative genes. Pharmacological blockade of YAP and TEA domain family member 1 (TEAD1) interaction rescued the mutant phenotypes. Taken together, Kdf1 mutation compromised murine amelogenesis through adhesion defects and subsequent Hippo-YAP dysregulation.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987454","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}

{"title":"Osteoblast-derived CAR3 synergizing with collagen and bone sialoprotein enhances bone formation.","authors":"Xiaoxin Ma, Qing He, Chen Ye, Jinglun Zhang, Xinyi Zhou, Yuxuan Zhang, Tian Gan, Zhe Li, Fangfang Song, Yufeng Zhang","doi":"10.1038/s41368-026-00443-6","DOIUrl":"10.1038/s41368-026-00443-6","url":null,"abstract":"<p><p>Osteoblasts orchestrate the infiltration and crystallization of mineral precursors within collagen fibrils. Certain osteoblast-secreted mineralization-inducing proteins further stimulate bone formation. In this study, scRNA-seq analysis of murine skull and long bone revealed a striking expression pattern of carbonic anhydrase III (Car3) in osteoblasts. We uncovered a pivotal role for CAR3 in osteoblast lineage cells, revealing its critical function in skeletal development and homeostasis. Conditional ablation of Car3 in Prx1-lineage cells resulted in osteopenia and markedly impaired osteoblast activity, underscoring its functional role. Mechanistically, the primary transcription factor RUNX2 directly regulated Car3 expression, mediating its spatiotemporal expression during development. Notably, CAR3 promoted collagen intrafibrillar mineralization by forming a ternary complex with COL1A1 and bone sialoprotein (BSP), thereby facilitating mineral deposition. Furthermore, CAR3-functionalized scaffolds significantly improved bone repair and regeneration by promoting both matrix mineralization and recruitment of Prx1-lineage cells. These findings establish CAR3 as a critical coordinator of osteoblast differentiation and collagen interfibrillar mineralization, positioning it as a central mediator for maintaining skeletal integrity and enabling regeneration.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972428","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}

{"title":"Fuel to fire: developmental niche-empowered ApoEVs unlock adult hierarchical tissue regenerative potential via mitochondrial complex I-driven developmental metabolic profile.","authors":"Yanshu Zhang, Jieyun Xu, Yuhan Shi, Yihua Cai, Mixiao Gui, Junlong Xue, Xuan Zhou, Ziqiong Qin, Hongcheng Chen, Guanqi Liu, Songtao Shi, Xueli Mao, Zetao Chen","doi":"10.1038/s41368-026-00440-9","DOIUrl":"10.1038/s41368-026-00440-9","url":null,"abstract":"<p><p>Organ defects involving hierarchical tissue structures remain a major challenge due to limited regenerative capacity in adulthood. To break this bottleneck, regenerative medicine is undergoing a paradigm shift from simulating the healing process of mature organs to reactivating re-development potential, namely developmental engineering strategy. In this study, we propose a novel paradigm based on developmental niche-empowered stem cell-derived apoptotic extracellular vesicles (DevNiche-ApoEVs), which integrates cues from both parental stem cells and their environmental niches. Using the periodontium as a classical hierarchical model, we identified developmental M2-phenotype macrophages (DevM2φ) as a key niche component that induces a developmental metabolic profile in stem cells, characterized by enhanced energy metabolism, mitochondrial homeostasis, and dominance of oxidative phosphorylation. We subsequently empowered ApoEVs with DevM2φ-mediated developmental niche to generate DevNiche-ApoEVs capable of delivering mitochondrial complex I and recapitulating the developmental metabolic profile. In vitro studies confirmed DevNiche-ApoEVs reactivated the developmental potential of adult periodontal ligament cells (PDLCs), while complex I inhibition abrogated this effect. Consistently, DevNiche-ApoEVs promoted re-development-based hierarchical periodontal regeneration by recapitulating critical developmental events in vivo. This study highlights the pivotal role of the developmental niche in hierarchical tissue regeneration and provides a promising DevNiche-ApoEVs-focused developmental engineering strategy, which offers both a solid theoretical foundation and an effective translational solution to overcome the longstanding bottleneck in adult tissue regeneration.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874107","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}

{"title":"Machine learning-driven discovery of therapeutic nucleoside hydrogels for periodontitis.","authors":"Weiqi Li, Yinghui Wen, Zhenyuan Huang, Fangyuan Shuai, Yijia Yin, Qianming Chen, Fudong Zhu, Hao Xu, Hang Zhao","doi":"10.1038/s41368-026-00438-3","DOIUrl":"10.1038/s41368-026-00438-3","url":null,"abstract":"<p><p>Supramolecular hydrogels hold significant potential in drug delivery and tissue engineering, with standing out for their unique properties. Despite their promise, predicting nucleoside bioactivity remains challenging. This study aims to predict the biological activity of nucleosides to guide the rational synthesis of hydrogels. Specifically, nine predictive models and databases for various biological activities were built with feature-selected machine learning methods including decision trees, logistic regression, random forest, and extreme gradient boosting. Then, the Molecular Bioactivity Specificity Index (MBSI) was introduced to gauge the primary bioactivity of nucleoside derivatives, and the Composite Molecular Attribute Score (CMAS) was devised to measure the overall performance of nucleoside derivatives. Subsequently, screening strategies for bioactive nucleoside hydrogels were established, and two candidate hydrogels (GMP and dGMP) with high hydrogel-forming ability, biocompatibility, and antibacterial activity were identified. Finally, two hydrogels were validated for antibacterial treatment of periodontitis. This study highlights the feasibility of ML-based strategies and MBSI/CMAS in rationally designing bioactive nucleoside hydrogels for biomedical applications. The discovery of GMP and dGMP hydrogels and their successful validation in periodontitis models highlight the potential of this strategy for developing targeted therapies for oral diseases.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874113","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}

{"title":"DNA framework-based nanomedicine platform: a triple-function strategy for treating periodontitis via antibacterial, anti-inflammatory, and osteogenesis-promoting activities.","authors":"Geru Zhang, Weitong Cui, Haoyan Wu, Xiaowei Liu, Liwei Huang, Yunfeng Lin, Xiaoxiao Cai","doi":"10.1038/s41368-026-00439-2","DOIUrl":"10.1038/s41368-026-00439-2","url":null,"abstract":"<p><p>Periodontitis is the most prevalent chronic inflammatory condition affecting oral health and is associated with long treatment duration. It is triggered by microbial plaque, which leads to localized and diffuse inflammation, ultimately causing progressive and irreversible damage to the alveolar bone and connective tissue. Therefore, early and effective treatment strategies should prioritize both antimicrobial and anti-inflammatory interventions. Herein, we report a multifunctional DNA nanodrug delivery platform based on tetrahedral framework nucleic acids (tFNAs), which effectively delivers curcumin and defensin to periodontal tissues. This platform exhibits a triple therapeutic effect by eliminating periodontal pathogenic bacteria, reducing inflammatory infiltration in periodontal tissues, and inhibiting bone resorption and degradation. Experimental results showed that curcumin was uniformly loaded onto the framework nucleic acid via groove binding, while defensin was anchored via chemical conjugation, forming the curcumin-defensin-tFNA (Cur-de-tFNA) complex. Due to its structural advantages, this nanodrug platform demonstrates exceptional cellular uptake efficiency and biosafety, significantly enhancing the bioavailability of curcumin and the antimicrobial activity of defensin. Moreover, as the platform degrades into nucleic acids, it presents one of the cleanest nanodrug delivery platforms currently available. As anticipated, the complex demonstrated potent antimicrobial activity, modulated the TLR4 pathway, improved the local microenvironment, promoted the expression of osteogenic proteins, and alleviated local tissue inflammation in a rat model of periodontitis, effectively reducing alveolar bone resorption. We believe that this study offers meaningful insights for multi-targeted combination therapies for periodontitis and provides new directions for the management of bacterial infection-induced local inflammation and bone resorption-related diseases.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771084","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}

{"title":"Mutational signature-based classification uncovers emerging oral cancer subtypes with distinct molecular patterns.","authors":"Sophie Deneuve,Béatrice Fervers,Julia S Bruno,Emma Bach,Sergey Senkin,Gabrielle Goldman-Lévy,Christine Carreira,Israa Laklouk,Rong Hu,Liacine Bouaoun,Olivia Pérol,Bérénice Chavanel,Lingeng Lu,Taja Lozar,Tarik Gheit,Paul F Lambert,Isabelle Coste,Toufic Renno,Jiri Zavadil,François Virard","doi":"10.1038/s41368-026-00437-4","DOIUrl":"https://doi.org/10.1038/s41368-026-00437-4","url":null,"abstract":"Tobacco use, alcohol consumption, and infection with human papilloma virus (HPV) are well-established risk factors for head and neck squamous cell carcinomas (HNSCC). However, the incidence of oral cancer, particularly in the mobile tongue, has been rising in non-smoker/non-drinker and HPV-negative patients, suggesting the emergence of a new clinical entity. To understand in molecular terms this subtype of oral cavity squamous cell carcinomas (OCSCC) with no-identified risk factor (NIRF), we analyzed the available public head and neck cancer multi-omics data. We identified mutational signatures that stratified 253 OCSCC and 94 laryngeal cancer cases, used as tobacco-only-related controls, according to their clinico-pathological characteristics. We show that tobacco, depending on the anatomical site, triggers distinct mutational processes and further demonstrate that the single-base-substitution (SBS) signature SBS16 in OCSCC is associated with tobacco smoking, reflecting the combined effects of smoking and drinking. Importantly, we identified a tongue cancer-enriched NIRF OCSCC subgroup exhibiting significantly increased endogenous clock-like mutagenesis, while another NIRF subgroup manifested with elevated apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC)-associated mutagenesis. Both NIRF OCSCC subgroups harbored specific cancer driver mutations and distinct methylation patterns, which differed from those observed in OCSCC linked to traditional HNSCC risk factors, reflecting unique molecular programs underlying disease development. Specifically, NIRF-OSCC exhibited pronounced immune evasion strategies and antimicrobial transcriptomic responses. Our study presents the first molecular and genomic characterization of the emerging NIRF OCSCC subtype likely driven by increased endogenous mutagenesis and responses to microbial insults. These findings warrant future detailed investigations into etiology and have implications for clinical management and cancer prevention.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"4 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738995","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":"Single-cell multi-omics sequencing reveals cell-specific transcriptomic and chromatin accessibility profiles in gut microbiome metabolite butyrate-produced pain modulation.","authors":"Ran Tao,Sufang Liu,Joshua Crawford,Phillip Kramer,Steven Bender,Feng Tao","doi":"10.1038/s41368-026-00432-9","DOIUrl":"https://doi.org/10.1038/s41368-026-00432-9","url":null,"abstract":"Pain is the most common symptom of temporomandibular joint (TMJ) disorders, which present significant clinical challenges due to their complexity and limited treatment options. Our previous study demonstrates that gut microbiome-derived butyrate is critical for the modulation of TMJ pain. In this study, we investigated its underlying mechanisms, and we found that oral administration of tributyrin, a prodrug of butyrate, not only significantly alleviated TMJ pain but also reversed the reduction in histone acetylation in the spinal trigeminal nucleus caudalis (Sp5C) under the TMJ pain condition. Using single-cell multi-omics sequencing, we profiled gene expression and chromatin accessibility in the Sp5C cells at the single-cell resolution. Bioinformatics analysis revealed that TMJ pain disrupted both the expression and chromatin accessibility of Nop14, Matk, Idh3b, Ndst2, and Tomm6 across four cell types in the Sp5C, and these alterations were reversed by tributyrin treatment. Specifically, Nop14 exhibited increased chromatin accessibility at its promoter region under TMJ pain condition, and knockdown of Nop14 in the Sp5C restored histone acetylation and alleviated TMJ pain. Together, our findings reveal cell-type-specific gene regulation that underlies butyrate-mediated epigenetic regulation of TMJ pain, which suggesting that targeting gut microbiome metabolites could develop a non-opioid novel therapy for TMJ disorders.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"1 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147702216","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}