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Experts consensus on the procedure of dental operative microscope in endodontics and operative dentistry. 牙科手术显微镜在牙髓病学和牙科手术中的应用达成共识。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-18 DOI: 10.1038/s41368-023-00247-y
Bin Liu, Xuedong Zhou, Lin Yue, Benxiang Hou, Qing Yu, Bing Fan, Xi Wei, Lihong Qiu, Zhengwei Huang, Wenwei Xia, Zhe Sun, Hanguo Wang, Liuyan Meng, Bin Peng, Chen Zhang, Shuli Deng, Zhaojie Lu, Deqin Yang, Tiezhou Hou, Qianzhou Jiang, Xiaoli Xie, Xuejun Liu, Jiyao Li, Zuhua Wang, Haipeng Lyu, Ming Xue, Jiuyu Ge, Yi Du, Jin Zhao, Jingping Liang

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.

牙科手术显微镜已广泛应用于牙科领域,特别是在根管学和手术牙科中,在根管治疗、根管外科和牙齿修复的有效性方面取得了重大进展。然而,这种显微镜的不当使用在临床环境中仍然很常见,主要是由于操作员对这种设备的功能和既定操作程序的理解和熟练程度不足。2019年10月,中华口腔医学会牙病与牙髓学学会副理事长梁静平教授组织召开了一次与中国牙髓病和手术牙科专家的共识会议。这次会议的目的是为牙科手术显微镜建立一个标准的操作程序。随后,各方达成共识并正式发布。在大约四年的时间里,这一共识的内容通过实践经验得到了进一步发展和完善。
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引用次数: 0
Maxillary sinus floor augmentation: a review of current evidence on anatomical factors and a decision tree. 上颌窦底增强术:对解剖学因素和决策树的现有证据的回顾。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-15 DOI: 10.1038/s41368-023-00248-x
Mingyue Lyu, Dingyi Xu, Xiaohan Zhang, Quan Yuan

Maxillary sinus floor augmentation using lateral window and crestal technique is considered as predictable methods to increase the residual bone height; however, this surgery is commonly complicated by Schneiderian membrane perforation, which is closely related to anatomical factors. This article aimed to assess anatomical factors on successful augmentation procedures. After review of the current evidence on sinus augmentation techniques, anatomical factors related to the stretching potential of Schneiderian membrane were assessed and a decision tree for the rational choice of surgical approaches was proposed. Schneiderian membrane perforation might occur when local tension exceeds its stretching potential, which is closely related to anatomical variations of the maxillary sinus. Choice of a surgical approach and clinical outcomes are influenced by the stretching potential of Schneiderian membrane. In addition to the residual bone height, clinicians should also consider the stretching potential affected by the membrane health condition, the contours of the maxillary sinus, and the presence of antral septa when evaluating the choice of surgical approaches and clinical outcomes.

采用侧窗和嵴技术提高上颌窦底被认为是可预测的增加残余骨高度的方法;然而,该手术常并发施耐德膜穿孔,这与解剖学因素密切相关。本文旨在评估成功隆胸手术的解剖学因素。在回顾了目前关于鼻窦增强技术的证据后,我们评估了与施耐德膜拉伸潜力相关的解剖学因素,并提出了一个合理选择手术入路的决策树。当局部张力超过其拉伸电位时,可能发生施耐德膜穿孔,这与上颌窦的解剖变异密切相关。施耐德膜的拉伸电位影响手术入路的选择和临床结果。除了残余骨高度外,临床医生在评估手术入路选择和临床结果时,还应考虑受膜健康状况、上颌窦轮廓和室间隔存在影响的拉伸潜力。
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引用次数: 0
Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development. 青蒿素通过抑制白念珠菌菌丝的发育来抑制口腔念珠菌病。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-12 DOI: 10.1038/s41368-023-00245-0
Xiaoyue Liang, Ding Chen, Jiannan Wang, Binyou Liao, Jiawei Shen, Xingchen Ye, Zheng Wang, Chengguang Zhu, Lichen Gou, Xinxuan Zhou, Lei Cheng, Biao Ren, Xuedong Zhou

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

白色念珠菌是口腔中最丰富的真菌种类。作为一种聪明的机会致病菌,它通过从酵母菌到菌丝的转变来增加毒力,成为口腔念珠菌病的主要致病菌。然而,目前临床抗真菌药物的过度使用和新型药物的缺乏突出了抗真菌治疗的挑战,因为它的耐药性和副作用。抗毒策略已被证明是开发新型抗感染药物的可行途径。本研究利用青蒿素、双氢青蒿素、青蒿酸、双氢青蒿酸、青蒿琥酯、蒿醚和蒿醚等7种青蒿素靶向白色念珠菌最重要的毒力因子菌丝发育。青蒿素对白色念珠菌(包括临床抗唑菌株)的生长没有影响,但能显著抑制菌丝发育,降低其对口腔上皮细胞的损伤,其中青蒿素的作用最强。转录组分析表明,青蒿素可能影响白色念珠菌的能量代谢。结果表明,7种青蒿素均能显著抑制ATP和cAMP的产生,同时降低了RAS1过表达菌株对菌丝的抑制作用,表明青蒿素通过调控RAS1 -cAMP- efg1通路抑制菌丝的发育。重要的是,青蒿醚显著抑制氟康唑敏感和耐药菌株引起的小鼠口咽念珠菌病模型体内真菌负荷和感染,无全身毒性。我们的研究结果首次表明,青蒿素可能是潜在的抗白色念珠菌感染的化合物,其目标是其菌丝的发育。
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引用次数: 0
Publisher Correction: The interaction between the nervous system and the stomatognathic system: from development to diseases. 出版者更正:神经系统与口颌系统的相互作用:从发育到疾病。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-11 DOI: 10.1038/s41368-023-00250-3
Yuzhu Wu, Yanhua Lan, Jiajie Mao, Jiahui Shen, Ting Kang, Zhijian Xie
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引用次数: 0
Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma. 单细胞转录组学分析揭示了腮腺多形性腺瘤的起源和瘤内异质性。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-07 DOI: 10.1038/s41368-023-00243-2
Xiuyun Xu, Jiaxiang Xie, Rongsong Ling, Shengqi Ouyang, Gan Xiong, Yanwen Lu, Bokai Yun, Ming Zhang, Wenjin Wang, Xiqiang Liu, Demeng Chen, Cheng Wang

Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36+ myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36+ myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.

多形性腺瘤(PA)是唾液腺中最常见的良性肿瘤,具有高度的形态复杂性。然而,PA的起源和肿瘤内异质性在很大程度上是未知的。在这里,我们在单细胞分辨率下构建了PA的综合图谱,并显示PA表现出五个肿瘤亚群,三个再现正常腮腺的上皮状态,以及两个肿瘤特有的PA特异性上皮细胞(PASE)群体。然后,鉴定出6个PASE细胞亚群,它们在上皮、骨、免疫、代谢、干性和细胞周期特征上存在差异。此外,我们发现CD36+肌上皮细胞是PA的肿瘤启动细胞(tic),并由PI3K-AKT通路主导。靶向PI3K-AKT通路可显著抑制CD36+肌上皮细胞衍生的肿瘤球和PA类器官的生长。我们的研究结果为PA的多样性和起源提供了新的见解,为靶向PI3K-AKT信号通路治疗PA提供了重要的临床意义。
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引用次数: 1
Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism. 敲低PGC1α通过重编程能量代谢抑制口腔角化细胞增殖。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-04 DOI: 10.1038/s41368-023-00242-3
Yunkun Liu, Nengwen Huang, Xianghe Qiao, Zhiyu Gu, Yongzhi Wu, Jinjin Li, Chengzhou Wu, Bo Li, Longjiang Li

Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.

口腔潜在恶性疾病(OPMDs)是口腔鳞状细胞癌(OSCC)的前体。细胞能量代谢失调是癌细胞的一个重要标志。过氧化物酶体增殖体激活受体- γ辅激活因子-1 α (PGC1α)在线粒体能量代谢中起重要作用。然而,PGC1α在OPMDs进展中的分子机制尚不清楚。因此,我们从细胞增殖、细胞周期、细胞凋亡、异种移植肿瘤、线粒体DNA (mtDNA)、线粒体电子传递链复合物(ETC)、活性氧(ROS)、氧耗率(OCR)、细胞外酸化率(ECAR)和葡萄糖摄取等方面全面研究了PGC1α下调对人口腔角化不良细胞(DOKs)的影响。我们发现,敲低PGC1α可显著抑制DOKs体外增殖和体内肿瘤生长,诱导s期阻滞,抑制PI3K/Akt信号通路,但不影响细胞凋亡。机制上,PGC1α下调可降低mtDNA、ETC和OCR,同时通过调节乳酸脱氢酶A (LDHA)增强ROS、葡萄糖摄取、ECAR和糖酵解。此外,SR18292(一种PGC1α抑制剂)诱导DOKs氧化磷酸化功能障碍,并减缓DOK异种移植肿瘤的进展。因此,我们的研究表明,PGC1α通过重编程能量代谢和干扰能量代谢,在细胞增殖中起着至关重要的作用,是OPMDs的潜在治疗靶点。
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引用次数: 1
Divergent chondro/osteogenic transduction laws of fibrocartilage stem cell drive temporomandibular joint osteoarthritis in growing mice. 纤维软骨干细胞驱动生长小鼠颞下颌关节骨性关节炎的不同软骨/成骨转导规律
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-08-25 DOI: 10.1038/s41368-023-00240-5
Ruiye Bi, Qianli Li, Haohan Li, Peng Wang, Han Fang, Xianni Yang, Yiru Wang, Yi Hou, Binbin Ying, Songsong Zhu

The anterior disc displacement (ADD) leads to temporomandibular joint osteoarthritis (TMJOA) and mandibular growth retardation in adolescents. To investigate the potential functional role of fibrocartilage stem cells (FCSCs) during the process, a surgical ADD-TMJOA mouse model was established. From 1 week after model generation, ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis (OA)-like joint cartilage degeneration, manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis. Lineage tracing using Gli1-CreER+; Tmfl/-mice and Sox9-CreER+;Tmfl/-mice showed that ADD interfered with the chondrogenic capacity of Gli1+ FCSCs as well as osteogenic differentiation of Sox9+ lineage, mainly in the middle zone of TMJ cartilage. Then, a surgically induced disc reposition (DR) mouse model was generated. The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice. And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment. In conclusion, ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage, resulting in cartilage degeneration and loss of subchondral bone homeostasis, finally causing TMJ growth retardation. DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.

前盘移位(ADD)可导致青少年颞下颌关节骨性关节炎(TMJOA)和下颌发育迟缓。为了研究纤维软骨干细胞(FCSCs)在这一过程中的潜在功能作用,我们建立了ADD-TMJOA手术小鼠模型。从模型生成后1周开始,ADD小鼠下颌生长迟缓加重,伴骨关节炎(OA)样关节软骨变性,表现为软骨分化受损,软骨下骨稳态丧失。Gli1-CreER+的谱系追踪Tmfl/-小鼠和Sox9- creer +;Tmfl/-小鼠显示,ADD干扰Gli1+ FCSCs的成软骨能力以及Sox9+谱系的成骨分化,主要发生在TMJ软骨的中间区。然后,建立手术诱导的椎间盘复位(DR)小鼠模型。DR治疗可显著缓解adhd小鼠fscs的抑制能力。DR治疗后,adhd小鼠和青少年adhd患者OA表型均明显缓解,髁突生长明显改善。综上所述,ADD-TMJOA可导致软骨祖细胞能力和FCSCs谱系成骨分化受损,导致软骨退变和软骨下骨稳态丧失,最终导致TMJ生长迟缓。早期DR能明显缓解软骨退变,恢复TMJ软骨生长潜能。
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引用次数: 0
Atp6i deficient mouse model uncovers transforming growth factor-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation. Atp6i缺陷小鼠模型揭示转化生长因子-β1 /Smad2/3是调节成牙细胞分化和牙根形成的关键信号通路。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-08-21 DOI: 10.1038/s41368-023-00235-2
Jue Wang, Abigail McVicar, Yilin Chen, Hong-Wen Deng, Zhihe Zhao, Wei Chen, Yi-Ping Li

The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice (Atp6i-/-) arrested tooth root formation, indicated by truncated Hertwig's epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation. Atp6i-/- mice had largely decreased expression of odontoblast differentiation marker gene expression profiles (Col1a1, Nfic, Dspp, and Osx) in the alveolar bone. Atp6i-/- mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i-/- odontoblasts. Through treating pulp precursor cells with Atp6i-/- or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression (Nfic, Dspp, Osx, and Runx2). This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i-/- OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i-/- mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.

调控牙根发育和成牙细胞分化的生物分子机制尚不清楚。我们发现,Atp6i缺陷小鼠(Atp6i-/-)阻止了牙根的形成,这表明Hertwig's上皮根鞘(HERS)的进展被截断。此外,Atp6i缺乏显著降低了负责根形成的根状牙原细胞的增殖和分化。Atp6i-/-小鼠牙槽骨中成牙细胞分化标记基因(Col1a1、Nfic、Dspp和Osx)的表达显著降低。Atp6i-/-小鼠样本RNA-seq分析结果显示成牙细胞标记物表达水平下降。此外,Smad2/3激活显著降低,抑制Atp6i-/-成牙细胞中转化生长因子-β (TGF-β)信号传导。通过用Atp6i-/-或野生型OC骨吸收条件培养基处理牙髓前体细胞,我们发现后者能促进成牙髓细胞分化,表现为成牙髓细胞分化标记基因(Nfic、Dspp、Osx和Runx2)表达增加。这种增加的表达被抗tgf -β1抗体中和显著阻断,而Atp6i-/- OC条件培养基显著减弱成牙细胞分化和Smad2/3的激活。重要的是,异位TGF-β1部分挽救了Atp6i-/-小鼠牙胚在小鼠肾胶囊下移植的根发育和根本质沉积。总之,我们的新数据表明,OC功能障碍阻止了TGF-β1从牙槽骨基质中释放,可能会通过受损的根状成牙细胞分化导致骨质疏松相关的根形成。因此,本研究发现TGF-β1 /Smad2/3是调节成牙细胞分化和牙根形成的关键信号通路,可能有助于未来牙根再生的治疗方法。
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引用次数: 0
The interaction between the nervous system and the stomatognathic system: from development to diseases. 神经系统与口颌系统的相互作用:从发育到疾病。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-08-15 DOI: 10.1038/s41368-023-00241-4
Yuzhu Wu, Yanhua Lan, Jiajie Mao, Jiahui Shen, Ting Kang, Zhijian Xie

The crosstalk between the nerve and stomatognathic systems plays a more important role in organismal health than previously appreciated with the presence of emerging concept of the "brain-oral axis". A deeper understanding of the intricate interaction between the nervous system and the stomatognathic system is warranted, considering their significant developmental homology and anatomical proximity, and the more complex innervation of the jawbone compared to other skeletons. In this review, we provide an in-depth look at studies concerning neurodevelopment, craniofacial development, and congenital anomalies that occur when the two systems develop abnormally. It summarizes the cross-regulation between nerves and jawbones and the effects of various states of the jawbone on intrabony nerve distribution. Diseases closely related to both the nervous system and the stomatognathic system are divided into craniofacial diseases caused by neurological illnesses, and neurological diseases caused by an aberrant stomatognathic system. The two-way relationships between common diseases, such as periodontitis and neurodegenerative disorders, and depression and oral diseases were also discussed. This review provides valuable insights into novel strategies for neuro-skeletal tissue engineering and early prevention and treatment of orofacial and neurological diseases.

随着“脑-口轴”概念的出现,神经和口颌系统之间的相互作用在机体健康中发挥着比以前认识到的更重要的作用。考虑到神经系统和口颌系统在发育上的同源性和解剖学上的接近性,以及颌骨与其他骨骼相比更复杂的神经支配,有必要对神经系统和口颌系统之间复杂的相互作用有更深入的了解。在这篇综述中,我们提供了一个深入的研究关于神经发育,颅面发育和先天性异常发生时,这两个系统发育异常。综述了神经与颌骨的交叉调节以及颌骨的不同状态对骨内神经分布的影响。与神经系统和口颌系统密切相关的疾病分为由神经系统疾病引起的颅面疾病和由异常的口颌系统引起的神经系统疾病。讨论了牙周炎、神经退行性疾病等常见病与抑郁症、口腔疾病之间的双向关系。这一综述为神经骨骼组织工程的新策略以及早期预防和治疗口面部和神经系统疾病提供了有价值的见解。
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引用次数: 1
LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling. LITTIP/Lgr6/HnRNPK复合体通过Wnt信号调控骨水泥形成。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-08-09 DOI: 10.1038/s41368-023-00237-0
Tiancheng Li, Han Wang, Yukun Jiang, Shuo Chen, Danyuan Huang, Zuping Wu, Xing Yin, Chenchen Zhou, Yuyu Li, Shujuan Zou

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.

正畸诱导牙根吸收(OIRR)是正畸治疗中的一个严重并发症。刺激骨水泥修复是治疗OIRR的基本方法。甲状旁腺激素(PTH)可能是治疗OIRR的潜在药物,但其作用仍缺乏直接证据,其潜在机制尚不清楚。本研究旨在探索长链非编码rna (lncRNAs)在介导间歇性甲状旁腺激素的合成代谢作用和促进骨质修复中的潜在参与,因为确定lncrna与疾病的关联可以为疾病的诊断和治疗提供有价值的见解。在这里,我们发现间歇性PTH通过调节Wnt通路调节永生化小鼠成水泥细胞OCCM-30的细胞增殖和矿化。在体内,每天给药PTH足以通过局部抑制Wnt/β-catenin信号传导来加速根再生。通过RNA芯片分析,鉴定出lncRNA LITTIP(间歇性PTH下LGR6基因间转录物)是间歇性PTH下骨水泥形成的关键调控因子。通过RNA纯化(ChIRP)和RNA免疫沉淀(RIP)分离染色质发现,LITTIP与富含亮氨酸的重复g蛋白偶联受体6 (LGR6)和异质核核糖核蛋白K (HnRNPK)蛋白的mRNA结合。进一步共转染实验证实,LITTIP在LITTIP/Lgr6/HnRNPK复合物的形成中发挥了结构作用。此外,LITTIP能够通过rna结合蛋白HnRNPK促进LGR6的表达。总的来说,我们的研究结果表明间歇性PTH通过抑制Wnt途径加速根再生。lncRNA LITTIP通过HnRNPK促进LGR6的高表达激活Wnt/β-catenin信号通路,负向调控骨水泥形成。
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International Journal of Oral Science
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