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Emerging roles of exosomes in oral diseases progression. 外泌体在口腔疾病进展中的新作用。
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-01-15 DOI: 10.1038/s41368-023-00274-9
Jiayi Wang, Junjun Jing, Chenchen Zhou, Yi Fan

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.

牙周炎、唾液腺疾病和口腔癌等口腔疾病对患者的消化功能、发音和审美要求产生了不利影响,极大地挑战了患者的健康状况。延迟诊断和非针对性治疗深刻影响着患者的预后和生活质量。探索早期检测和精确治疗的创新方法是口腔医学的一个前景广阔的前沿领域。外泌体是一种纳米级的细胞外囊泡,几乎所有类型的细胞都会分泌外泌体。随着研究的不断深入,这些源于细胞内的细胞外囊泡在生物过程中的复杂作用逐渐展现出来。外泌体作为有价值的诊断和治疗工具备受关注,因为它们能够转移丰富的生物载体,并在多种细胞功能中发挥错综复杂的作用。在这篇综述中,我们概述了外泌体在口腔疾病领域的最新应用,重点关注与炎症相关的骨病和口腔鳞状细胞癌。我们描述了外泌体改变的特征,并展示了它们作为早期诊断生物标记物的潜在应用,强调了它们在多种口腔疾病中作为指标的作用。我们还总结了外泌体在靶向治疗中的应用前景,并提出了将外泌体用于临床治疗的未来方向。
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引用次数: 0
Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement. 力诱导的 Caspase-1 依赖性裂解调节正畸牙齿的移动。
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-01-15 DOI: 10.1038/s41368-023-00268-7
Liyuan Chen, Huajie Yu, Zixin Li, Yu Wang, Shanshan Jin, Min Yu, Lisha Zhu, Chengye Ding, Xiaolan Wu, Tianhao Wu, Chunlei Xun, Yanheng Zhou, Danqing He, Yan Liu

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.

裂解是一种依赖于炎性卡巴酶的程序性细胞死亡,在维持组织稳态和激活炎症反应方面发挥着重要作用。正畸牙齿移动(OTM)是一种无菌力诱导的炎性骨重塑过程,由牙周韧带(PDL)祖细胞激活介导。然而,外力是否以及如何诱导牙周韧带祖细胞热解,从而影响 OTM 和牙槽骨重塑仍是未知数。在这项研究中,我们发现机械力能诱导大鼠 OTM 和牙槽骨重塑过程中热凋亡相关标志物的表达。阻断或提高热凋亡水平可分别抑制或促进 OTM 和牙槽骨重塑。利用Caspase-1-/-小鼠,我们进一步证实了PDL祖细胞受力诱导的热凋亡的功能作用依赖于Caspase-1。此外,机械力还能诱导人体内外力处理的PDL祖细胞和体外压缩力加载的PDL祖细胞发生热凋亡,从而影响破骨细胞的生成。从机理上讲,瞬时受体电位亚家族 V 成员 4 信号转导参与了力诱导的 Caspase-1 依赖性 PDL 祖细胞的破骨细胞生成。总之,这项研究提出了一种在机械刺激下调节破骨细胞生成和牙槽骨重塑的新机制,为通过靶向Caspase-1加速OTM提供了一种可行的方法。
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引用次数: 0
Omics for deciphering oral microecology Omics 解密口腔微生态学
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-01-09 DOI: 10.1038/s41368-023-00264-x
Yongwang Lin, Xiaoyue Liang, Zhengyi Li, Tao Gong, Biao Ren, Yuqing Li, Xian Peng

The human oral microbiome harbors one of the most diverse microbial communities in the human body, playing critical roles in oral and systemic health. Recent technological innovations are propelling the characterization and manipulation of oral microbiota. High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes. New long-read platforms improve genome assembly from complex samples. Single-cell genomics provides insights into uncultured taxa. Advanced imaging modalities including fluorescence, mass spectrometry, and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution. Fluorescence techniques link phylogenetic identity with localization. Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification. Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches. Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly, gene expression, metabolites, microenvironments, virulence mechanisms, and microbe-host interfaces in the context of health and disease. However, significant knowledge gaps persist regarding community origins, developmental trajectories, homeostasis versus dysbiosis triggers, functional biomarkers, and strategies to deliberately reshape the oral microbiome for therapeutic benefit. The convergence of sequencing, imaging, cultureomics, synthetic systems, and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict, prevent, diagnose, and treat associated oral diseases.

人类口腔微生物群是人体中最多样化的微生物群落之一,在口腔和全身健康中发挥着至关重要的作用。最近的技术创新推动了口腔微生物群的特征描述和操作。高通量测序技术实现了口腔微生物组的全面分类和功能分析。新的长读数平台改进了复杂样本的基因组组装。单细胞基因组学提供了对未培养类群的深入了解。包括荧光、质谱和拉曼光谱在内的先进成像模式使口腔微生物的空间组织和相互作用可视化的分辨率不断提高。荧光技术将系统发育特性与定位联系起来。质谱成像技术揭示了代谢壁龛和代谢活动,而拉曼光谱技术则能快速生成生物分子指纹进行分类。培养组学有助于利用高通量方法分离和培养新型快速口腔类群。这些技术的不断整合有望改变我们对口腔微生物组的组合、基因表达、代谢物、微环境、毒力机制以及健康和疾病背景下微生物-宿主界面的认识。然而,在群落起源、发育轨迹、平衡与菌群失调诱因、功能性生物标志物以及有意重塑口腔微生物群以获得治疗益处的策略等方面仍存在巨大的知识差距。测序、成像、培养组学、合成系统和生物仿真模型的融合将为口腔微生物组提供前所未有的洞察力,并为预测、预防、诊断和治疗相关口腔疾病提供机会。
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引用次数: 0
Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability. 牙周炎患者口腔微生物群的硝酸盐还原能力受损:对全身一氧化氮可用性的潜在影响。
IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-01-05 DOI: 10.1038/s41368-023-00266-9
Bob T Rosier, William Johnston, Miguel Carda-Diéguez, Annabel Simpson, Elena Cabello-Yeves, Krystyna Piela, Robert Reilly, Alejandro Artacho, Chris Easton, Mia Burleigh, Shauna Culshaw, Alex Mira

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity (NRC) and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals (P < 0.05 in all five datasets with n = 20-82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate (a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15 healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment (P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria (P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.

口腔微生物群将硝酸盐还原成亚硝酸盐的过程被认为对口腔健康非常重要,并能形成一氧化氮,从而改善心脏代谢状况。对龈下牙菌斑中细菌组成的研究表明,硝酸盐还原菌与牙周健康有关,但牙周炎对硝酸盐还原能力(NRC)的影响以及因此对一氧化氮可用性的影响尚未得到评估。本研究旨在评估牙周炎如何影响口腔微生物群的硝酸盐还原能力。首先,分析了来自五个不同国家的 16S rRNA 测序数据,发现牙周炎患者龈下菌斑中的硝酸还原菌明显低于健康人(P
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引用次数: 0
Neuroimaging and artificial intelligence for assessment of chronic painful temporomandibular disorders—a comprehensive review 用于评估慢性颞下颌关节疼痛性障碍的神经影像学和人工智能--综合评述
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2023-12-28 DOI: 10.1038/s41368-023-00254-z
Mayank Shrivastava, Liang Ye

Chronic Painful Temporomandibular Disorders (TMD) are challenging to diagnose and manage due to their complexity and lack of understanding of brain mechanism. In the past few decades’ neural mechanisms of pain regulation and perception have been clarified by neuroimaging research. Advances in the neuroimaging have bridged the gap between brain activity and the subjective experience of pain. Neuroimaging has also made strides toward separating the neural mechanisms underlying the chronic painful TMD. Recently, Artificial Intelligence (AI) is transforming various sectors by automating tasks that previously required humans’ intelligence to complete. AI has started to contribute to the recognition, assessment, and understanding of painful TMD. The application of AI and neuroimaging in understanding the pathophysiology and diagnosis of chronic painful TMD are still in its early stages. The objective of the present review is to identify the contemporary neuroimaging approaches such as structural, functional, and molecular techniques that have been used to investigate the brain of chronic painful TMD individuals. Furthermore, this review guides practitioners on relevant aspects of AI and how AI and neuroimaging methods can revolutionize our understanding on the mechanisms of painful TMD and aid in both diagnosis and management to enhance patient outcomes.

慢性颞下颌关节疼痛症(TMD)由于其复杂性和缺乏对大脑机制的了解,在诊断和治疗方面具有挑战性。在过去的几十年里,神经影像学研究已经阐明了疼痛调节和感知的神经机制。神经影像学的进步缩小了大脑活动与疼痛主观体验之间的差距。神经影像学在分离 TMD 慢性疼痛的神经机制方面也取得了长足进步。最近,人工智能(AI)正在改变各个领域,将以前需要人类智慧才能完成的任务自动化。人工智能已开始为识别、评估和理解疼痛性 TMD 做出贡献。人工智能和神经影像学在了解慢性疼痛 TMD 的病理生理学和诊断方面的应用仍处于早期阶段。本综述旨在确定当代神经影像学方法,如结构、功能和分子技术,这些方法已被用于研究慢性疼痛 TMD 患者的大脑。此外,本综述还将指导从业人员了解人工智能的相关方面,以及人工智能和神经影像学方法如何彻底改变我们对 TMD 疼痛机制的认识,并帮助诊断和管理以提高患者的治疗效果。
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引用次数: 0
Differential molecular profiles and associated functionalities characterize connective tissue grafts obtained at different locations and depths in the human palate 人腭不同位置和深度的结缔组织移植物具有不同的分子特征和相关功能特性
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2023-12-11 DOI: 10.1038/s41368-023-00260-1
Maria B. Asparuhova, Xiaoqing Song, Dominic Riedwyl, Geert van Geest, Dieter D. Bosshardt, Anton Sculean

The present study aimed to assess the molecular profiles of subepithelial connective tissue grafts (CTGs) obtained at different locations and depths in the human palate. Sixty-four CTGs belonging to anterior deep (AD), anterior superficial (AS), posterior deep (PD), and posterior superficial (PS) groups were subjected to RNA-Sequencing and their transcriptomes were analyzed computationally. Functional correlations characterizing the CTG groups were validated by cell biological experiments using primary human palatal fibroblasts (HPFs) extracted from the CTGs. A clearly more pronounced location-dependent than depth-dependent difference between the grafts, with a minimal number of genes (4) showing no dependence on the location, was revealed. Epithelial, endothelial, and monocytic cell migration was strongly (P < 0.001) potentiated by AD- and PS-HPFs. Moreover, significantly increased expression of genes encoding C-C and C-X-C motif chemokine ligands as well as significantly (P < 0.01) activated p38 signaling suggested immunomodulatory phenotype for AD- and PS-HPFs. Increased growth factor gene expression and significantly activated (P < 0.001) Erk and Akt signaling in HPFs originating from A-CTGs implied their involvement in cell survival, proliferation, and motility. Prominent collagen-rich expression profile contributing to high mechanical stability, increased osteogenesis-related gene expression, and strongly activated (P < 0.001) Smad1/5/8 signaling characterized HPFs originating from P-CTGs. The present data indicate that in humans, differences between palatal CTGs harvested from different locations and depths appear to be location- rather than depth-dependent. Our findings provide the basis for future personalization of the therapeutic strategy by selecting an optimal graft type depending on the clinical indications.

本研究旨在评估人腭不同位置和深度的上皮下结缔组织移植物(CTG)的分子特征。研究人员对属于前深(AD)、前浅(AS)、后深(PD)和后浅(PS)组的64个CTG进行了RNA测序,并对其转录组进行了计算分析。使用从 CTGs 提取的原代人腭成纤维细胞(HPFs)进行细胞生物学实验,验证了 CTG 组的功能相关性特征。结果显示,移植物之间的差异明显取决于位置而非深度,只有极少数基因(4 个)与位置无关。上皮细胞、内皮细胞和单核细胞的迁移受到 AD-HPFs 和 PS-HPFs 的强烈促进(P < 0.001)。此外,编码 C-C 和 C-X-C motif 趋化因子配体的基因表达明显增加,p38 信号的激活也明显增加(P < 0.01),这表明 AD-HPFs 具有免疫调节表型。在源自 A-CTG 的 HPFs 中,生长因子基因表达增加,Erk 和 Akt 信号明显激活(P < 0.001),这意味着它们参与了细胞的存活、增殖和运动。源自 P-CTG 的 HPF 具有显著的富含胶原蛋白的表达谱,这有助于提高机械稳定性、增加成骨相关基因的表达以及强烈激活(P < 0.001)Smad1/5/8 信号传导。本研究数据表明,在人类中,从不同位置和深度采集的腭CTG之间的差异似乎与位置而非深度有关。我们的研究结果为今后根据临床适应症选择最佳移植类型的个性化治疗策略奠定了基础。
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引用次数: 0
Oral administration of Bifidobacterium breve improves anti-angiogenic drugs-derived oral mucosal wound healing impairment via upregulation of interleukin-10 口服双歧杆菌可通过上调白细胞介素-10改善抗血管生成药物引起的口腔黏膜伤口愈合障碍
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2023-12-11 DOI: 10.1038/s41368-023-00263-y
Qingxiang Li, Yuke Li, Qiao Qiao, Ning Zhao, Yuanning Yang, Lin Wang, Yifei Wang, Chuanbin Guo, Yuxing Guo

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.

最近的研究表明,长期应用抗血管生成药物可能会损害口腔黏膜伤口愈合。本研究探讨了舒尼替尼对小鼠口腔黏膜愈合障碍的影响以及前列双歧杆菌(B. breve)的治疗潜力。小鼠硬腭粘膜缺损模型用于研究舒尼替尼和/或唑来膦酸钠对伤口愈合的影响。通过微型计算机断层扫描(micro-CT)评估了粘膜缺损下骨的体积和密度。通过蛋白质芯片分析和酶联免疫吸附试验(ELISA)检测炎症因子。用舒尼替尼处理的口腔黏膜干细胞(OMSCs)的衰老和生物功能进行了测试。接合环实验用于研究口服布氏杆菌的影响。使用白细胞介素-10(IL-10)的中和抗体证明了IL-10在前列茵促愈合过程中的关键作用。结果显示,舒尼替尼导致小鼠口腔黏膜伤口愈合受损。在体外,舒尼替尼诱导 OMSCs 细胞衰老,并影响增殖、迁移和分化等生物功能。通过肠道树突状细胞(DCs)产生的IL-10,口服布瑞韦能减轻口腔黏膜炎症并促进伤口愈合。IL-10能逆转舒尼替尼导致的OMSCs细胞衰老,IL-10中和抗体能阻断布氏酵母菌在舒尼替尼治疗条件下对口腔黏膜伤口愈合的改善作用。总之,舒尼替尼可诱导OMSCs细胞衰老并导致口腔黏膜伤口愈合受损,而口服布氏杆菌可通过肠道DCs衍生的IL-10改善伤口愈合受损。
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引用次数: 0
Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral 成人牙齿上皮干细胞衍生的器官组织沉积羟基磷灰石生物矿物质
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2023-12-07 DOI: 10.1038/s41368-023-00257-w
Hyun-Yi Kim, Victoria Cooley, Eun-Jung Kim, Shujin Li, Jong-Min Lee, Dina Sheyfer, Wenjun Liu, Ophir D. Klein, Derk Joester, Han-Sung Jung

Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.

釉母细胞是源自牙齿上皮的特化细胞,可产生釉质,釉质是一种由高度拉长的羟基磷灰石(OHAp)结晶体组成的分层结构组织。上皮细胞合成结晶并将其组装成机械坚固结构的独特功能尚未完全阐明,部分原因是体外实验模型的局限性。在此,我们证明了从小鼠门牙组织中分离出的成牙上皮干细胞(aDESCs)生成矿化牙上皮器官组织(DEOs)的能力。DEOs表达成釉细胞标记,可在含有Wnt、Egf、Bmp、Fgf和Notch信号通路调节剂的培养基中体外维持5个月(11次传代)以上,并适合低温保存。当移植到小鼠肾囊下时,器官组织产生的OHAp结晶在成分、大小和形状上与矿化牙齿组织相似,包括一些类似珐琅质的细长结晶。因此,DEOs是研究牙齿上皮矿化过程的强大体外模型,可为了解釉质形成和开发釉质再生疗法铺平道路。
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引用次数: 0
Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia. 抗成纤维细胞生长因子 23 疗法对 X 连锁低磷血症患者牙齿的影响
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2023-12-06 DOI: 10.1038/s41368-023-00259-8
Elis J Lira Dos Santos, Kenta Nakajima, Julien Po, Ayako Hanai, Volha Zhukouskaya, Martin Biosse Duplan, Agnès Linglart, Takashi Shimada, Catherine Chaussain, Claire Bardet

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg-1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.

X连锁低磷血症(XLH)中成纤维细胞生长因子23(FGF23)的升高会导致佝偻病和磷酸盐消耗,表现为严重的骨骼和牙齿异常。Burosumab是一种FGF23中和抗体,可替代常规治疗(磷和活性维生素D类似物),对长骨表型有显著改善。在此,我们研究了 FGF23 抗体(FGF23-mAb)是否也能改善与 XLH 相关的齿槽特征。四周大的雄性 Hyp 小鼠每周注射 4 或 16 mg-kg-1 的 FGF23-mAb 达 2 个月,并与野生型(WT)和药物(PBS)治疗的 Hyp 小鼠(n = 3-7 只)进行比较。显微 CT 分析表明,两种剂量的 FGF23-mAb 都能恢复 Hyp 小鼠的牙本质/牙釉质体积,并纠正扩大的牙髓体积,较高浓度的 FGF23-mAb 能产生与 WT 水平相似的修复效果。与用药物治疗的小鼠相比,FGF23-mAb 还能改善牙槽骨体积分数和矿物质密度。组织学检查显示,牙槽骨组织的矿化程度有所提高,类骨质、predentin 和 cementoid 的数量有所减少。牙周韧带附着情况也有所改善,无细胞骨水泥的恢复就是证明。这些临床前数据与对两名 XLH 患者的回顾性分析结果一致,显示布罗苏单抗治疗可改善口腔特征。总之,我们的数据表明,FGF23-mAb 治疗能极大地改善牙槽组织,预示着它在牙科异常临床治疗中的益处。
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引用次数: 0
Expert consensus on digital guided therapy for endodontic diseases. 牙髓疾病数字引导治疗专家共识。
IF 14.9 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2023-12-06 DOI: 10.1038/s41368-023-00261-0
Xi Wei, Yu Du, Xuedong Zhou, Lin Yue, Qing Yu, Benxiang Hou, Zhi Chen, Jingping Liang, Wenxia Chen, Lihong Qiu, Xiangya Huang, Liuyan Meng, Dingming Huang, Xiaoyan Wang, Yu Tian, Zisheng Tang, Qi Zhang, Leiying Miao, Jin Zhao, Deqin Yang, Jian Yang, Junqi Ling

Digital guided therapy (DGT) has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades. The concept of DGT for endodontic diseases is categorized into static guided endodontics (SGE), necessitating a meticulously designed template, and dynamic guided endodontics (DGE), which utilizes an optical triangulation tracking system. Based on cone-beam computed tomography (CBCT) images superimposed with or without oral scan (OS) data, a virtual template is crafted through software and subsequently translated into a 3-dimensional (3D) printing for SGE, while the system guides the drilling path with a real-time navigation in DGE. DGT was reported to resolve a series of challenging endodontic cases, including teeth with pulp obliteration, teeth with anatomical abnormalities, teeth requiring retreatment, posterior teeth needing endodontic microsurgery, and tooth autotransplantation. Case reports and basic researches all demonstrate that DGT stand as a precise, time-saving, and minimally invasive approach in contrast to conventional freehand method. This expert consensus mainly introduces the case selection, general workflow, evaluation, and impact factor of DGT, which could provide an alternative working strategy in endodontic treatment.

近几十年来,数字引导治疗(Digital guided therapy,DGT)作为一种治疗牙髓疾病的现代计算机辅助技术得到了广泛推广。数字引导根管治疗的概念分为静态引导根管治疗(SGE)和动态引导根管治疗(DGE),前者需要精心设计模板,后者则利用光学三角追踪系统。在锥形束计算机断层扫描(CBCT)图像的基础上,叠加或不叠加口腔扫描(OS)数据,通过软件制作虚拟模板,随后转化为三维(3D)打印,用于 SGE,而在 DGE 中,系统通过实时导航引导钻孔路径。据报道,DGT 解决了一系列具有挑战性的牙髓病例,包括牙髓阻塞的牙齿、解剖异常的牙齿、需要再治疗的牙齿、需要进行牙髓显微手术的后牙以及牙齿自体移植。病例报告和基础研究都表明,与传统的徒手方法相比,DGT 是一种精确、省时和微创的方法。本专家共识主要介绍了 DGT 的病例选择、一般工作流程、评估和影响因素,它可以为牙髓治疗提供另一种工作策略。
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International Journal of Oral Science
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