International Journal of Oral Science最新文献

H3K18la in periodontal ligament fibroblasts regulates immune niches and alveolar bone remodeling under mechanical loads 牙周韧带成纤维细胞中的H3K18la调节机械负荷下的免疫龛和牙槽骨重塑

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2026-10-02 DOI: 10.1038/s41368-026-00465-0

Bo Zhang, Zhihang Song, Yige Zhang, Jingyi Cai, Guanyin Zhu, Zhihe Zhao

{"title":"H3K18la in periodontal ligament fibroblasts regulates immune niches and alveolar bone remodeling under mechanical loads","authors":"Bo Zhang, Zhihang Song, Yige Zhang, Jingyi Cai, Guanyin Zhu, Zhihe Zhao","doi":"10.1038/s41368-026-00465-0","DOIUrl":"https://doi.org/10.1038/s41368-026-00465-0","url":null,"abstract":"The metabolism and remodeling of alveolar bone are highly active, which dynamically respond to mechanical force. However, the mechanism of how alveolar bone responds to mechanical force remains elusive. Orthodontics is essentially a physiological process of mechanical force–driven alveolar bone remodeling. Here, we demonstrated that orthodontic tension promoted the expression of glycolysis-related genes in periodontal ligament (PDL) fibroblasts. The mechanoactivated glycolysis subsequently enhanced lactylation on histone H3 lysine 18 (H3K18la) in PDL fibroblasts. CUT&Tag analysis revealed that H3K18la was enriched at the promoter region of CXCL1 to upregulate its transcription. 3PO inhibited glycolysis and attenuated stretching force–induced H3K18la and CXCL1 levels in PDL fibroblasts. CXCL1 subsequently augmented oxidative phosphorylation in macrophages and promoted M2 macrophage polarization. Additionally, in vivo inhibition of glycolysis by periodontal injection of 3PO disrupted the CXCL1-mediated CXCR2+ macrophage infiltration and inhibited bone formation during orthodontic tooth movement. Furthermore, the blockade of the CXCL1/CXCR2 axis in vivo, using Cxcr2 knockout (Cxcr2–/–) mice, impaired tension–induced M2 macrophage polarization in PDL, disrupting the pro-resolving microenvironment conducive to bone formation during orthodontic tooth movement. Overall, the results reveal that the tension–induced glycolysis–H3K18la axis in PDL fibroblasts plays a critical role in creating the pro-resolving periodontal immune niche and facilitating alveolar bone formation during orthodontic tooth movement.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"1 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087816","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

Spatially resolved single cell atlas deciphers SAA1 inflammatory epithelial cells. 空间分辨单细胞图谱破译SAA1炎性上皮细胞。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-09-29 DOI: 10.1038/s41368-026-00464-1

Yajie Wu, Zhifei Su, Bowen Zhang, Fangjie Zhou, Ranhui Xi, Xian Peng, Yuqing Li, Lin Yue, Xiaoyan Wang, Feng Chen, Yao Lu, Xuedong Zhou, Biao Ren, Jiyao Li

{"title":"Spatially resolved single cell atlas deciphers SAA1 inflammatory epithelial cells.","authors":"Yajie Wu, Zhifei Su, Bowen Zhang, Fangjie Zhou, Ranhui Xi, Xian Peng, Yuqing Li, Lin Yue, Xiaoyan Wang, Feng Chen, Yao Lu, Xuedong Zhou, Biao Ren, Jiyao Li","doi":"10.1038/s41368-026-00464-1","DOIUrl":"10.1038/s41368-026-00464-1","url":null,"abstract":"Disruption of epithelial integrity is a pivotal event in inflammation, disease pathogenesis, and tissue homeostasis. To investigate these processes in chronic inflammatory disease, we performed spatial transcriptomics integrated with single-cell RNA sequencing (scRNA-seq) on human gingival tissue, coupled with metagenomic analysis of matched subgingival plaque. This approach allowed in situ characterization of epithelial heterogeneity and microbiome-epithelium-connective tissue crosstalk. We identified a distinct inflammatory epithelial subpopulation (SAA1+Epi), situated within the junctional epithelium, that becomes activated through the TLR2-PITX2 axis by Porphyromonas gingivalis lipopolysaccharide. These SAA1+Epi cells secrete TGFβ, which induces an inflammatory program in the connective tissue by driving the differentiation of inflammation-associated fibroblasts (C3+FB) via the PI3K/Akt pathway. Concurrently, SAA1+Epi cells express chemotactic factors such as CXCL6 to recruit NK cells, thereby sustaining the inflammatory niche. The transcription factor PITX2 emerged as a critical regulator of SAA1+Epi differentiation; targeting PITX2 suppressed C3+FB induction and natural killer (NK) cells recruitment, ultimately attenuating periodontitis progression. Our findings position SAA1+Epi as a frontline responder to dysbiotic bacteria at the inflammatory interface and underscore its essential role in regulating epithelial-connective tissue homeostasis during inflammation.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074590","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

RUNX2 promotes osteoclast differentiation and bone resorption via the newly identified LncRNA-ROD: implications for alveolar remodeling. RUNX2通过新发现的LncRNA-ROD促进破骨细胞分化和骨吸收：对肺泡重塑的影响。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-09-28 DOI: 10.1038/s41368-026-00466-z

Jie Li, Yang Liu, Yanchun Qiao, Changqing Yan, Weiwei Zhao, Lingli Ji, Dandan Liu, Yuejiao Xin, Chenying Zhang, Xiaozhe Wang, Yixiang Wang, Shuguo Zheng

{"title":"RUNX2 promotes osteoclast differentiation and bone resorption via the newly identified LncRNA-ROD: implications for alveolar remodeling.","authors":"Jie Li, Yang Liu, Yanchun Qiao, Changqing Yan, Weiwei Zhao, Lingli Ji, Dandan Liu, Yuejiao Xin, Chenying Zhang, Xiaozhe Wang, Yixiang Wang, Shuguo Zheng","doi":"10.1038/s41368-026-00466-z","DOIUrl":"10.1038/s41368-026-00466-z","url":null,"abstract":"Delayed tooth eruption is a hallmark of cleidocranial dysplasia (CCD) caused by RUNX2 haploinsufficiency, yet the underlying molecular mechanism remains undefined. Here, we show that RUNX2 regulates osteoclast-mediated alveolar bone remodeling, a process closely associated with tooth eruption. Runx2+/- mice exhibit impaired osteoclast differentiation and reduced alveolar bone resorption, resulting in delayed mandibular molar eruption-a phenotype that recapitulates human CCD. Mechanistically, RUNX2 transcriptionally activates LncRNA-ROD (Regulator of Osteoclast Differentiation), which promotes osteoclastogenesis by sequestering QKI to stabilize Csf1r mRNA. LncRNA-ROD-/- mice phenocopy the eruption defects and reduced alveolar bone resorption observed in Runx2+/- mice. Critically, both Runx2+/- and LncRNA-ROD-/- mice show reduced osteoclast differentiation in alveolar bone, consistent with in vitro data from bone marrow-derived monocytes/macrophages demonstrating impaired osteoclast differentiation. Notably, rescue experiments in ovariectomy-induced osteoporosis models demonstrate that QKI knockdown restores osteoclast differentiation in Runx2+/- and LncRNA-ROD-/- mice, highlighting the critical role of the RUNX2/LncRNA-ROD/QKI axis in osteoclastogenesis. The axis supports alveolar bone remodeling associated with tooth eruption. These results provide mechanistic insights into cleidocranial dysplasia-related alveolar bone remodeling defects and delayed tooth eruption, and identify LncRNA-ROD as a potential therapeutic target for alveolar bone remodeling disorders. Furthermore, this axis is implicated in broader bone metabolic disorders, as demonstrated by its impact on osteoporosis progression in Runx2+/- and LncRNA-ROD-/- mice.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074600","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

IGFBP5 alleviates periodontitis by reversing human dental follicle stem cell senescence via the non-canonical Wnt pathway. IGFBP5通过非典型Wnt通路逆转人牙滤泡干细胞衰老，从而缓解牙周炎。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-09-15 DOI: 10.1038/s41368-026-00463-2

Yuru Wang, Yue Wang, Yuguo Dai, Weihua Guo, Jun Liu

{"title":"IGFBP5 alleviates periodontitis by reversing human dental follicle stem cell senescence via the non-canonical Wnt pathway.","authors":"Yuru Wang, Yue Wang, Yuguo Dai, Weihua Guo, Jun Liu","doi":"10.1038/s41368-026-00463-2","DOIUrl":"10.1038/s41368-026-00463-2","url":null,"abstract":"The improvement of health and the delay of aging represent pivotal goals in medical research. Bone aging contributes to various age-related disorders, including periodontitis. Dental follicle stem cells (DFSCs) serve as ideal seed cells for periodontal regenerative therapy. Insulin-like growth factor binding protein 5 (IGFBP5) has been reported to exert complex and context-dependent effects. However, its role in DFSC senescence remains undefined. In this study, we observed a significant decrease in IGFBP5 expression in DFSCs undergoing replicative or H₂O₂-induced senescence. Functional experiments demonstrated that IGFBP5 overexpression alleviated cellular senescence and enhanced osteogenic potential, a process linked to the modulation of non-canonical Wnt signaling. WNT5B was then identified as a potential downstream regulator involved in mediating the pro-osteogenic effects of IGFBP5. To translate these findings clinically, we developed Gel-vHA@oe-DFSC, a nanoparticle-embedded hydrogel system for cell delivery, which enhanced the therapeutic efficacy of DFSCs and promoted periodontal regeneration in a rat model. Collectively, our study reveals a novel function of IGFBP5 in mitigating DFSC senescence and presents a promising strategy for combating periodontal bone loss.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968728","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

ID3-directed sonogenetics to enhance osteogenesis and bone defect healing. id3定向超声遗传学促进骨生成和骨缺损愈合。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-09-14 DOI: 10.1038/s41368-026-00456-1

Huan Liu, Yifan Xu, Xue Wang, Meijing Liu, Jinsong Wang, Sijia Na, Xiaogang Wang, Songlin Wang, Lei Hu

{"title":"ID3-directed sonogenetics to enhance osteogenesis and bone defect healing.","authors":"Huan Liu, Yifan Xu, Xue Wang, Meijing Liu, Jinsong Wang, Sijia Na, Xiaogang Wang, Songlin Wang, Lei Hu","doi":"10.1038/s41368-026-00456-1","DOIUrl":"10.1038/s41368-026-00456-1","url":null,"abstract":"Sonogenetics, a noninvasive approach combining ultrasound physics with genetic engineering, has shown clinical potential in promoting bone repair. However, its therapeutic efficacy remains suboptimal due to the scarcity of bone-specific ultrasound-responsive targets and insufficient modulation of osteogenic signaling pathways. Herein, we investigated the role of the transcriptional repressor inhibitor of DNA binding/differentiation 3 (Id3) in bridging sonogenetics and bone regeneration. RNA sequencing and PCR array analyses revealed significant downregulation of Id3 during low-intensity pulsed ultrasound (LIPUS)-induced bone formation, suggesting Id3 acts as a \"brake\" on ultrasound-mediated osteogenesis. As a member of the ID protein family, Id3 binds to basic helix-loop-helix (bHLH) transcription factors (e.g., E-proteins) to suppress their DNA-binding capacity and osteogenic gene transcription-particularly in bone marrow-derived mesenchymal stem cells (BMSCs), a key cell type for bone repair. Functional experiments demonstrated that Id3 knockdown enhanced LIPUS-induced osteogenic differentiation of BMSCs in vitro (upregulating RUNX2, OCN) and promoted in vivo bone formation in rodent bone defect models, while Id3 overexpression reversed these effects. Chromatin immunoprecipitation (ChIP) assays confirmed that Id3 directly targets bHLH proteins to inhibit the Bmp/Smad pathway, a core cascade for osteogenesis. Based on these findings, we propose an ID3-based sonogenetic strategy: we engineered an Id3-inhibitory peptide (rID3) targeting the Id3/E2A interface, which would synergize with LIPUS to enhance defect healing of cranial bone. Our work delineates a novel CaN/NFATC3/Id3/E2A/Bmp4 pathway for ultrasound mechanobiology and provides a promising combinatorial therapeutic strategy for precision sonogenetics bone regeneration.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963041","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

Piezo channels contribute to the terminal cytodifferentiation of odontoblasts via modulation of canonical Wnt signaling. 压电通道通过调节典型的Wnt信号传导促进成牙细胞的终末细胞分化。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-09-10 DOI: 10.1038/s41368-026-00461-4

Xuguang Nie, Kelley Huang, Emily Chu, Man-Kyo Chung

{"title":"Piezo channels contribute to the terminal cytodifferentiation of odontoblasts via modulation of canonical Wnt signaling.","authors":"Xuguang Nie, Kelley Huang, Emily Chu, Man-Kyo Chung","doi":"10.1038/s41368-026-00461-4","DOIUrl":"10.1038/s41368-026-00461-4","url":null,"abstract":"Piezo1 and Piezo2 are mechanosensitive ion channels that transduce mechanical stimuli into intracellular biochemical signals in diverse tissues and organ systems. Their functions in odontoblast development are still not well understood. In this study, we showed that Piezo1 and Piezo2 displayed dynamic expression in odontoblasts during terminal cytodifferentiation, suggesting a functional role in this process. However, Piezo1 knockouts in odontoblasts using Wnt1-Cre (Piezo1 cKO) did not cause pronounced structural change in tooth development in a majority of the Piezo1 cKO mice. Piezo2 cKO did not show obvious tooth defect either. Therefore, we pursued a double knockout approach. A phenotype analysis of Wnt1-Cre mediated Piezo1 and Piezo2 double knockout (Piezo1/Piezo2 dKO) mice revealed impaired cytodifferentiation and morphological change in the odontoblasts. Specifically, the heights of odontoblast and ameloblast layers were lower in Piezo1/Piezo2 dKO mice than controls, and expression of markers for odontoblast terminal differentiation, including collagen type 1a and alkaline phosphatase, was delayed. Furthermore, levels of nuclear β-catenin and Wnt10a were remarkably decreased, indicative of compromised Wnt/β-catenin signaling. Notably, the application of the Wnt10a protein rescued the odontoblast phenotype of Piezo1/Piezo2 dKO teeth in an ex vivo organ culture system. Moreover, the intraperitoneal injection of Yoda1, a Piezo1 channel agonist, facilitated odontoblast cytodifferentiation and elevated Wnt/β-catenin signaling in dental pulp tissues at the newborn stage. Altogether, these data suggest that Piezo channels play a role in regulating the terminal differentiation of odontoblasts via modulation of Wnt/β-catenin signaling.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919832","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

PFKM acts as a metabolic switch initiating donut-shaped mitochondrial remodeling to promote osteogenesis. PFKM作为一种代谢开关，启动甜甜圈形状的线粒体重塑，促进成骨。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-08-31 DOI: 10.1038/s41368-026-00460-5

Nengwen Huang, Yang Li, Jie Lu, Yifeng Xing, Weiping Chen, Kaidi Chen, Geyuan Zheng, Pengyuan Hu, Kaixun He, Hanyu Lin, Wenxiu Yuan, Yuwei Zhou, Zhenzhu Xue, Junjin Lin, Wen Li, Sihui Zhang, Yanjing Ou, Jiang Chen

{"title":"PFKM acts as a metabolic switch initiating donut-shaped mitochondrial remodeling to promote osteogenesis.","authors":"Nengwen Huang, Yang Li, Jie Lu, Yifeng Xing, Weiping Chen, Kaidi Chen, Geyuan Zheng, Pengyuan Hu, Kaixun He, Hanyu Lin, Wenxiu Yuan, Yuwei Zhou, Zhenzhu Xue, Junjin Lin, Wen Li, Sihui Zhang, Yanjing Ou, Jiang Chen","doi":"10.1038/s41368-026-00460-5","DOIUrl":"10.1038/s41368-026-00460-5","url":null,"abstract":"Osteogenic differentiation requires sophisticated mitochondrial adaptation to meet bioenergetic demands, yet regulatory checkpoints governing this organelle reorganization remain poorly defined. Through single-cell RNA sequencing reanalysis and metabolic intervention, this study unveils a non-canonical signaling role for PFKM, traditionally recognized solely as a glycolytic enzyme, in orchestrating mitochondrial remodeling during bone formation. Beyond its established metabolic function, Pfkm suppression triggers distinctive donut-shaped mitochondria through a novel signaling cascade. Mechanistically, Pfkm knockdown expands mitochondria-endoplasmic reticulum contacts (MERCs), facilitating mitochondrial calcium influx. Concomitantly, elevated CD38 suppresses protein kinase A (PKA) activity, inducing DRP1 dephosphorylation at Serine 656. This signaling integration promotes DRP1 mitochondrial translocation, driving the characteristic donut architecture. This structural transformation initiates comprehensive mitochondrial quality control (MQC) encompassing enhanced biogenesis, selective mitophagy, and mitochondrial-derived vesicles (MDVs) secretion, collectively optimizing the osteogenic microenvironment and cellular mineralization capacity. In vivo validation demonstrates that AAV-mediated Pfkm knockdown accelerates bone repair in rat calvarial and femoral defect models. This work establishes PFKM as a dual-function regulator bridging metabolism and mitochondrial signaling, offering a potent therapeutic avenue for bone regeneration.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864911","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

Mechanical control in dental and jaw morphogenesis and remodeling. 牙颌形态发生与重塑的机械控制。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-08-31 DOI: 10.1038/s41368-026-00462-3

Xiangjun Yang, Xiaotian Zhang, Qingping Gao, Songlin Wang, Xiaoshan Wu

{"title":"Mechanical control in dental and jaw morphogenesis and remodeling.","authors":"Xiangjun Yang, Xiaotian Zhang, Qingping Gao, Songlin Wang, Xiaoshan Wu","doi":"10.1038/s41368-026-00462-3","DOIUrl":"10.1038/s41368-026-00462-3","url":null,"abstract":"Tooth and maxillomandibular bone development is a synergistic process precisely and coordinately regulated by genetic programs, molecular signaling networks, and external environmental factors. Recent rapid progress in in situ biomechanical measurement techniques, cellular mechanical imaging, and molecular tracing technologies has greatly promoted research in developmental biomechanics. Accumulating evidence indicates that mechanical stimuli can be converted into biochemical signals via cellular mechanotransduction pathways, thereby modulating key cellular processes, including proliferation, differentiation, and apoptosis, and further regulating tissue morphogenesis and remodeling. In this review, we focus on the role of mechanical control in dental and jaw morphogenesis and remodeling. We first summarize the sources and spatiotemporal distribution features of mechanical stress during dentofacial development. Subsequently, we elaborate on the regulatory roles and underlying molecular mechanisms of mechanical signals in key dentofacial developmental processes, including crown development, root morphogenesis, tooth eruption and replacement, as well as maxillomandibular bone development and remodeling. Finally, we discuss the current research gaps in the field of mechanical stress regulation of dentofacial development and propose potential future research directions.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864881","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

Mechanobiology of orofacial tissues: principles, mechanisms, and therapeutic applications. 口腔面部组织的机械生物学：原理、机制和治疗应用。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-08-27 DOI: 10.1038/s41368-026-00458-z

Junnan Qi, Yawen Wang, Yuandong Xie, Wenjie Ma, Yi Li, Xiaoduo Tang, Hongchen Sun, Bei Chang

{"title":"Mechanobiology of orofacial tissues: principles, mechanisms, and therapeutic applications.","authors":"Junnan Qi, Yawen Wang, Yuandong Xie, Wenjie Ma, Yi Li, Xiaoduo Tang, Hongchen Sun, Bei Chang","doi":"10.1038/s41368-026-00458-z","DOIUrl":"10.1038/s41368-026-00458-z","url":null,"abstract":"The orofacial system is constantly subjected to complex and dynamic mechanical forces and exhibits highly specialized mechanosensory and mechanoresponsive behaviors. However, current studies are mostly limited to single tissues or specific pathway analyses, which are insufficient to reveal a comprehensive mechanoregulation network. Here, we propose a three-dimensional integrative framework of mechanobiology to systematically characterize oral tissue responses across three interconnected levels: (1) mechanical microenvironment and tissue-specific responses (phenomenological level); (2) molecular regulatory networks driven by mechanical stimuli (mechanistic level); and (3) therapeutic strategies informed by mechanical cues (translational level). Guided by this framework, we delineated an evolutionary trajectory in the design of mechanoresponsive biomaterials, from passive mechanical compliance to active mechanoregulation and ultimately to intelligent, self-adaptive systems, which may offer a reframed perspective for orofacial regenerative medicine. Furthermore, this review provides a preliminary exploration of the potential link between the oral mechanical environment and systemic health, suggesting the potential to inspire future research on oral intervention strategies targeting systemic diseases. Moreover, by summarizing the current advancements, we highlight that future endeavors should focus on key challenges, such as the development of real-time monitoring technologies, the inspiration of smart responsive materials, and the establishment of clinical translation standards. Collectively, this review offers an integrative conceptual framework for understanding the mechanical regulation mechanisms in orofacial tissues and provides new insights for next-generation tissue engineering strategies.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840357","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

TLR9-engineered photoresponsive biomimetic nanodecoys for targeted NETs clearance to mitigate periodontitis-associated bone resorption. tlr9工程的光响应仿生纳米诱饵，用于靶向net清除，减轻牙周炎相关的骨吸收。

IF 17.6 1区医学

International Journal of Oral Science Pub Date : 2026-08-25 DOI: 10.1038/s41368-026-00454-3

Siyan Liu, Yitong Liu, Yingyi Chen, Yao Jiao, Rui Zhao, Yijia Wang, Jiebing Zhang, Shuang Zhang, Yi Liu, Lijia Guo

{"title":"TLR9-engineered photoresponsive biomimetic nanodecoys for targeted NETs clearance to mitigate periodontitis-associated bone resorption.","authors":"Siyan Liu, Yitong Liu, Yingyi Chen, Yao Jiao, Rui Zhao, Yijia Wang, Jiebing Zhang, Shuang Zhang, Yi Liu, Lijia Guo","doi":"10.1038/s41368-026-00454-3","DOIUrl":"10.1038/s41368-026-00454-3","url":null,"abstract":"Periodontitis is a widespread and multifactorial inflammatory disease, that leads to the progressive destruction of periodontal tissues and resorption of alveolar bone. The treatment of periodontitis is complicated by complex interactions between the host and oral microbiota, as well as difficulties in obtaining satisfactory treatment effects. Although neutrophil extracellular traps (NETs) participate in the process of disease development induced by periodontitis, their persistent accumulation aggravates inflammatory injury and prevents regenerative processes. Therefore, on the basis of the identification of Toll-like receptor 9 (TLR9) as an important receptor for NETs recognition, a biomimetic and photoresponsive nanodecoy system was designed for the enhanced targeting and efficient degradation of NETs. Taking advantage of the inherent DNA-binding property of TLR9 and incorporating DNase I, this nanodecoy system was designed to drive effective NETs clearance. Under near-infrared radiation, the nanodecoys demonstrate photothermal properties to enhance the clearance of NETs and create an environment conducive to bone regeneration. Moreover, this design inhibits osteoclast overactivation and promotes osteoblast-mediated mineralization to modulate the bone remodeling process. These results demonstrate a promising targeted treatment strategy for periodontitis, which includes the targeting and clearance of NETs and inducing bone regeneration.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"18 1","pages":""},"PeriodicalIF":17.6,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818349","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