首页 > 最新文献

Journal of dental research最新文献

英文 中文
Autophagy Regulates Age-Related Jawbone Loss via LepR+ Stromal Cells. 自噬通过LepR+基质细胞调控与年龄相关的颌骨丧失
Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1177/00220345241264810
B Sun, Y Xu, H Wang, F Wang, Q Li, Y Chen, Z Wang

Bone aging and decreased autophagic activity are related but poorly explored in the jawbone. This study aimed to characterize the aging jawbones and jawbone-derived stromal cells (JBSCs) and determine the role of autophagy in jawbone mass decline. We observed that the jawbones of older individuals and mice exhibited similar age-related bone loss. Furthermore, leptin receptor (LepR)-lineage cells served as the primary source for in vitro cultured and expanded JBSCs, referred to as LepR-Cre+/JBSCs. RNA-sequencing data from the jawbones and LepR-Cre+/JBSCs showed the upregulated expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway during aging. Through single-cell transcriptomics, we identified a decrease in the proportion of osteogenic lineage cells and the activation of the PI3K/AKT pathway in LepR-lineage cells in aging bone tissues. Reduced basal autophagic activity, diminished autophagic flux, and decreased osteogenesis occurred in the jawbones and LepR-Cre+/JBSCs from older mice (O-mice; O-JBSCs). Pharmacologic and constitutive autophagy activation alleviated the impaired osteogenesis in O-JBSCs. In addition, the suppression of mTOR-induced autophagy improved the aging phenotype of O-JBSCs. The activation of autophagy in LepR-Cre+/JBSCs using chemical autophagic activators reduced the alveolar bone resorption in O-mice. Therefore, our study demonstrated that ATG molecules and pathways are crucial in jawbone aging, providing novel approaches to understanding age-related jawbone loss.

骨质老化与颌骨自噬活性降低有关,但在颌骨中的研究却很少。本研究旨在描述衰老的颌骨和颌骨衍生基质细胞(JBSCs)的特征,并确定自噬在颌骨质量下降中的作用。我们观察到,老年人和小鼠的颌骨表现出类似的与年龄相关的骨质流失。此外,瘦素受体(LepR)系细胞是体外培养和扩增 JBSCs(称为 LepR-Cre+/JBSCs)的主要来源。来自颌骨和LepR-Cre+/JBSCs的RNA测序数据显示,在衰老过程中,磷酸肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶标(mTOR)通路的表达上调。通过单细胞转录组学,我们发现在衰老的骨组织中,成骨系细胞比例下降,LepR系细胞的PI3K/AKT通路被激活。老年小鼠(O-mice;O-JBSCs)的颌骨和 LepR-Cre+/JBSCs 中出现了基础自噬活性降低、自噬通量减少和成骨减少的现象。药物和组成型自噬激活缓解了 O-JBSCs 中受损的成骨过程。此外,抑制 mTOR 诱导的自噬也改善了 O-JBSCs 的衰老表型。使用化学自噬激活剂激活 LepR-Cre+/JBSCs 的自噬可减少 O 型小鼠的牙槽骨吸收。因此,我们的研究证明 ATG 分子和通路在颌骨老化中至关重要,为了解与年龄相关的颌骨损失提供了新的方法。
{"title":"Autophagy Regulates Age-Related Jawbone Loss via LepR<sup>+</sup> Stromal Cells.","authors":"B Sun, Y Xu, H Wang, F Wang, Q Li, Y Chen, Z Wang","doi":"10.1177/00220345241264810","DOIUrl":"10.1177/00220345241264810","url":null,"abstract":"<p><p>Bone aging and decreased autophagic activity are related but poorly explored in the jawbone. This study aimed to characterize the aging jawbones and jawbone-derived stromal cells (JBSCs) and determine the role of autophagy in jawbone mass decline. We observed that the jawbones of older individuals and mice exhibited similar age-related bone loss. Furthermore, leptin receptor (LepR)-lineage cells served as the primary source for in vitro cultured and expanded JBSCs, referred to as LepR-Cre<sup>+</sup>/JBSCs. RNA-sequencing data from the jawbones and LepR-Cre<sup>+</sup>/JBSCs showed the upregulated expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway during aging. Through single-cell transcriptomics, we identified a decrease in the proportion of osteogenic lineage cells and the activation of the PI3K/AKT pathway in LepR-lineage cells in aging bone tissues. Reduced basal autophagic activity, diminished autophagic flux, and decreased osteogenesis occurred in the jawbones and LepR-Cre<sup>+</sup>/JBSCs from older mice (O-mice; O-JBSCs). Pharmacologic and constitutive autophagy activation alleviated the impaired osteogenesis in O-JBSCs. In addition, the suppression of mTOR-induced autophagy improved the aging phenotype of O-JBSCs. The activation of autophagy in LepR-Cre+/JBSCs using chemical autophagic activators reduced the alveolar bone resorption in O-mice. Therefore, our study demonstrated that ATG molecules and pathways are crucial in jawbone aging, providing novel approaches to understanding age-related jawbone loss.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1028-1038"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The PerioGene North Study Uncovers Serum Proteins Related to Periodontitis. PerioGene North 研究发现了与牙周炎有关的血清蛋白。
Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241263320
M Wänman, S Betnér, A Esberg, C K Holm, C Isehed, A Holmlund, P Palmqvist, A Lövgren, S Lindquist, L Hänström, U H Lerner, E Kindstedt, P Lundberg

The sequalae of periodontitis include irreversible degradation of tooth-supporting structures and circulatory spread of inflammatory mediators. However, the serum protein profile in periodontitis is not well described, which is partly attributable to the limited number of studies based on large and well-characterized periodontitis cohorts. This study aims to identify novel, circulating inflammation-related proteins associated with periodontitis within the PerioGene North case-control study, which includes 478 cases with severe periodontitis and 509 periodontally healthy controls. The serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and a panel of 45 inflammation-related proteins were analyzed using targeted proteomics. A distinguishable serum protein profile was evident in periodontitis cases. The protein pattern could separate cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve = 0.87). Adjusted levels for hs-CRP and 24 of the 45 proteins were different between cases and controls. High levels of hs-CRP and matrix metalloproteinase-12, and low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were detected among the cases. Furthermore, the levels of C-C motif chemokine-19, granulocyte colony-stimulating factor-3 (CSF-3), interleukin-7 (IL-7), and hs-CRP were significantly higher in cases with a high degree of gingival inflammation. The levels of CSF-3 and tumor necrosis factor ligand superfamily member-10 TNFSF-10 were higher in cases with many deep periodontal pockets. The PerioGene North study includes detailed clinical periodontal data and uncovers a distinct serum protein profile in periodontitis. The findings of lower EGF and OLR-1 among the cases are highlighted, as this has not been presented before. The role of EGF and OLR-1 in periodontitis pathogenesis and as possible future biomarkers should be further explored.

牙周炎的后遗症包括牙齿支持结构的不可逆退化和炎症介质的循环传播。然而,对牙周炎血清蛋白谱的描述并不完善,部分原因是基于大型、特征明确的牙周炎队列的研究数量有限。这项研究的目的是在 PerioGene North 病例对照研究(包括 478 例严重牙周炎病例和 509 例牙周健康对照组)中发现与牙周炎相关的新型循环炎症相关蛋白。研究采用靶向蛋白质组学分析了血清中高敏性 C 反应蛋白(hs-CRP)和 45 种炎症相关蛋白的浓度。牙周炎病例的血清蛋白特征明显不同。这种蛋白质模式可将病例与对照组区分开来,灵敏度为 0.81,特异性为 0.81(曲线下面积 = 0.87)。调整后的 hs-CRP 水平和 45 种蛋白质中的 24 种在病例和对照组之间存在差异。在病例中检测到高水平的 hs-CRP 和基质金属蛋白酶-12,以及低水平的表皮生长因子(EGF)和氧化低密度脂蛋白受体 1(OLR-1)。此外,在牙龈炎症程度较高的病例中,C-C 趋化因子-19、粒细胞集落刺激因子-3(CSF-3)、白细胞介素-7(IL-7)和 hs-CRP 的水平明显较高。在牙周袋较深的病例中,CSF-3 和肿瘤坏死因子配体超家族成员-10 TNFSF-10 的水平较高。PerioGene North 研究包括详细的临床牙周数据,并揭示了牙周炎中独特的血清蛋白特征。研究还特别强调了病例中 EGF 和 OLR-1 含量较低的发现,因为这种情况以前从未出现过。应进一步探讨 EGF 和 OLR-1 在牙周炎发病机制中的作用,并将其作为未来可能的生物标志物。
{"title":"The PerioGene North Study Uncovers Serum Proteins Related to Periodontitis.","authors":"M Wänman, S Betnér, A Esberg, C K Holm, C Isehed, A Holmlund, P Palmqvist, A Lövgren, S Lindquist, L Hänström, U H Lerner, E Kindstedt, P Lundberg","doi":"10.1177/00220345241263320","DOIUrl":"10.1177/00220345241263320","url":null,"abstract":"<p><p>The sequalae of periodontitis include irreversible degradation of tooth-supporting structures and circulatory spread of inflammatory mediators. However, the serum protein profile in periodontitis is not well described, which is partly attributable to the limited number of studies based on large and well-characterized periodontitis cohorts. This study aims to identify novel, circulating inflammation-related proteins associated with periodontitis within the PerioGene North case-control study, which includes 478 cases with severe periodontitis and 509 periodontally healthy controls. The serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and a panel of 45 inflammation-related proteins were analyzed using targeted proteomics. A distinguishable serum protein profile was evident in periodontitis cases. The protein pattern could separate cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve = 0.87). Adjusted levels for hs-CRP and 24 of the 45 proteins were different between cases and controls. High levels of hs-CRP and matrix metalloproteinase-12, and low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were detected among the cases. Furthermore, the levels of C-C motif chemokine-19, granulocyte colony-stimulating factor-3 (CSF-3), interleukin-7 (IL-7), and hs-CRP were significantly higher in cases with a high degree of gingival inflammation. The levels of CSF-3 and tumor necrosis factor ligand superfamily member-10 TNFSF-10 were higher in cases with many deep periodontal pockets. The PerioGene North study includes detailed clinical periodontal data and uncovers a distinct serum protein profile in periodontitis. The findings of lower EGF and OLR-1 among the cases are highlighted, as this has not been presented before. The role of EGF and OLR-1 in periodontitis pathogenesis and as possible future biomarkers should be further explored.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"999-1007"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineered 3D Periodontal Ligament Model with Magnetic Tensile Loading. 采用磁拉力加载的工程三维牙周韧带模型
Pub Date : 2024-09-01 Epub Date: 2024-08-26 DOI: 10.1177/00220345241264792
P Mulimani, N A Mazzawi, A J Goldstein, A M Obenaus, S M Baggett, D Truong, T E Popowics, N J Sniadecki

In vitro models are invaluable tools for deconstructing the biological complexity of the periodontal ligament (PDL). Model systems that closely reproduce the 3-dimensional (3D) configuration of cell-cell and cell-matrix interactions in native tissue can deliver physiologically relevant insights. However, 3D models of the PDL that incorporate mechanical loading are currently lacking. Hence, we developed a model where periodontal tissue constructs (PTCs) are made by casting PDL cells in a collagen gel suspended between a pair of slender, silicone posts for magnetic tensile loading. Specifically, one of the posts was rigid and the other was flexible with a magnet embedded in its tip so that PTCs could be subjected to tensile loading with an external magnet. Additionally, the deflection of the flexible post could be used to measure the contractile force of PDL cells in the PTCs. Prior to tensile loading, second harmonics generation analysis of collagen fibers in PTCs revealed that incorporation of PDL cells resulted in collagen remodeling. Biomechanical testing of PTCs by tensile loading revealed an elastic response at 4 h, permanent deformation by 1 d, and creep elongation by 1 wk. Subsequently, contractile forces of PDL cells were substantially lower for PTCs under tensile loading. Immunofluorescence analysis revealed that tensile loading caused PDL cells to increase in number, express higher levels of F-actin and α-smooth muscle actin, and become aligned to the tensile axis. Second harmonics generation analysis indicated that collagen fibers in PTCs progressively remodeled over time with tensile loading. Gene expression analysis also confirmed tension-mediated upregulation of the F-actin/Rho pathway and osteogenic genes. Our model is novel in demonstrating the mechanobiological behavior that results in cell-mediated remodeling of the PDL tissue in a 3D context. Hence, it can be a valuable tool to develop therapeutics for periodontitis, periodontal regeneration, and orthodontics.

体外模型是解构牙周韧带(PDL)生物复杂性的宝贵工具。模型系统可近似再现原生组织中细胞-细胞和细胞-基质相互作用的三维(3D)结构,从而提供与生理相关的见解。然而,目前还缺乏包含机械负荷的 PDL 三维模型。因此,我们开发了一种模型,通过在一对细长的硅胶柱之间悬浮的胶原凝胶中铸造 PDL 细胞来制作牙周组织构建体 (PTC),从而实现磁性拉伸加载。具体来说,其中一个硅胶柱是刚性的,另一个硅胶柱是柔性的,其顶端嵌入了磁铁,这样 PTC 就能承受外部磁铁的拉伸负荷。此外,柔性支柱的偏转可用于测量 PTC 中 PDL 细胞的收缩力。在拉伸加载之前,对 PTC 中的胶原纤维进行二次谐波生成分析,结果显示 PDL 细胞的加入导致了胶原重塑。通过拉伸加载对 PTC 进行的生物力学测试显示,4 小时后出现弹性反应,1 天后出现永久变形,1 周后出现蠕变伸长。随后,PDL 细胞在拉伸负荷下的收缩力大大低于 PTC。免疫荧光分析表明,拉伸负荷导致 PDL 细胞数量增加,表达更高水平的 F-肌动蛋白和 α 平滑肌肌动蛋白,并与拉伸轴对齐。二次谐波生成分析表明,随着时间的推移,PTCs 中的胶原纤维会随着拉伸负荷而逐渐重塑。基因表达分析也证实了张力介导的 F-actin/Rho 通路和成骨基因的上调。我们的模型在三维环境中展示了导致细胞介导的 PDL 组织重塑的机械生物学行为,具有新颖性。因此,它可以成为开发牙周炎、牙周再生和正畸疗法的重要工具。
{"title":"Engineered 3D Periodontal Ligament Model with Magnetic Tensile Loading.","authors":"P Mulimani, N A Mazzawi, A J Goldstein, A M Obenaus, S M Baggett, D Truong, T E Popowics, N J Sniadecki","doi":"10.1177/00220345241264792","DOIUrl":"10.1177/00220345241264792","url":null,"abstract":"<p><p>In vitro models are invaluable tools for deconstructing the biological complexity of the periodontal ligament (PDL). Model systems that closely reproduce the 3-dimensional (3D) configuration of cell-cell and cell-matrix interactions in native tissue can deliver physiologically relevant insights. However, 3D models of the PDL that incorporate mechanical loading are currently lacking. Hence, we developed a model where periodontal tissue constructs (PTCs) are made by casting PDL cells in a collagen gel suspended between a pair of slender, silicone posts for magnetic tensile loading. Specifically, one of the posts was rigid and the other was flexible with a magnet embedded in its tip so that PTCs could be subjected to tensile loading with an external magnet. Additionally, the deflection of the flexible post could be used to measure the contractile force of PDL cells in the PTCs. Prior to tensile loading, second harmonics generation analysis of collagen fibers in PTCs revealed that incorporation of PDL cells resulted in collagen remodeling. Biomechanical testing of PTCs by tensile loading revealed an elastic response at 4 h, permanent deformation by 1 d, and creep elongation by 1 wk. Subsequently, contractile forces of PDL cells were substantially lower for PTCs under tensile loading. Immunofluorescence analysis revealed that tensile loading caused PDL cells to increase in number, express higher levels of F-actin and α-smooth muscle actin, and become aligned to the tensile axis. Second harmonics generation analysis indicated that collagen fibers in PTCs progressively remodeled over time with tensile loading. Gene expression analysis also confirmed tension-mediated upregulation of the F-actin/Rho pathway and osteogenic genes. Our model is novel in demonstrating the mechanobiological behavior that results in cell-mediated remodeling of the PDL tissue in a 3D context. Hence, it can be a valuable tool to develop therapeutics for periodontitis, periodontal regeneration, and orthodontics.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1008-1016"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Visualization of Pulpal Structures by SWIR in Endodontic Access Preparation. 在牙髓通路制备过程中利用 SWIR 对牙髓结构进行可视化。
Pub Date : 2024-08-05 DOI: 10.1177/00220345241262949
L Benz, K Heck, D Hevisov, D Kugelmann, P-C Tseng, Z Sreij, F Litzenburger, J Waschke, F Schwendicke, A Kienle, R Hickel, K-H Kunzelmann, E Walter

Endodontic access preparation is one of the initial steps in root canal treatments and can be hindered by the obliteration of pulp canals and formation of tertiary dentin. Until now, methods for direct intraoperative visualization of the 3-dimensional anatomy of teeth have been missing. Here, we evaluate the use of shortwave infrared radiation (SWIR) for navigation during stepwise access preparation. Nine teeth (3 anteriors, 3 premolars, and 3 molars) were explanted en bloc with intact periodontium including alveolar bone and mucosa from the upper or lower jaw of human body donors. Analysis was performed at baseline as well as at preparation depths of 5 mm, 7 mm, and 9 mm, respectively. For reflection, SWIR was used at a wavelength of 1,550 nm from the occlusal direction, whereas for transillumination, SWIR was passed through each sample at the marginal gingiva from the buccal as well as oral side at a wavelength of 1,300 nm. Pulpal structures could be identified as darker areas approximately 2 mm before reaching the pulp chamber using SWIR transillumination, although they were indistinguishable under normal circumstances. Furcation areas in molars appeared with higher intensity than areas with canals. The location of pulpal structures was confirmed by superimposition of segmented micro-computed tomography (µCT) images. By radiomic analysis, significant differences between pulpal and parapulpal areas could be detected in image features. With hierarchical cluster analysis, both segments could be confirmed and associated with specific clusters. The local thickness of µCTs was calculated and correlated with SWIR transillumination images, by which a linear dependency of thickness and intensity could be demonstrated. Lastly, by in silico simulations of light propagation, dentin tubules were shown to be a crucial factor for understanding the visibility of the pulp. In conclusion, SWIR transillumination may allow direct clinical live navigation during endodontic access preparation.

根管通路准备是根管治疗的初始步骤之一,可能会受到牙髓管阻塞和第三牙本质形成的阻碍。到目前为止,还没有术中直接观察牙齿三维解剖结构的方法。在此,我们评估了短波红外线(SWIR)在分步通路准备过程中的应用。我们从人体捐献者的上颌或下颌取出九颗牙齿(3 颗前牙、3 颗前臼齿和 3 颗臼齿),连同完整的牙周膜(包括牙槽骨和粘膜)进行了整体移植。分别在基线以及制备深度为 5 毫米、7 毫米和 9 毫米时进行分析。反射时,使用波长为 1,550 nm 的西南红外光从咬合方向照射;透射时,使用波长为 1,300 nm 的西南红外光从颊侧和口侧穿过每个样本的边缘牙龈。使用西南红外透射光可以在到达牙髓腔前约 2 毫米处发现暗色区域的牙髓结构,尽管在正常情况下它们是无法区分的。磨牙的毛面区域比有牙槽骨的区域强度更高。牙髓结构的位置是通过叠加分割的微型计算机断层扫描(µCT)图像确认的。通过放射学分析,可以发现牙髓区和副牙髓区在图像特征上存在明显差异。通过分层聚类分析,可以确认这两个区段并与特定的聚类相关联。计算了 µCT 的局部厚度,并将其与西南红外透射图像相关联,从而证明了厚度与强度之间的线性关系。最后,通过对光传播进行硅模拟,证明牙本质小管是了解牙髓可见度的关键因素。总之,在牙髓通路准备过程中,SWIR 透射成像技术可以实现直接的临床现场导航。
{"title":"Visualization of Pulpal Structures by SWIR in Endodontic Access Preparation.","authors":"L Benz, K Heck, D Hevisov, D Kugelmann, P-C Tseng, Z Sreij, F Litzenburger, J Waschke, F Schwendicke, A Kienle, R Hickel, K-H Kunzelmann, E Walter","doi":"10.1177/00220345241262949","DOIUrl":"https://doi.org/10.1177/00220345241262949","url":null,"abstract":"<p><p>Endodontic access preparation is one of the initial steps in root canal treatments and can be hindered by the obliteration of pulp canals and formation of tertiary dentin. Until now, methods for direct intraoperative visualization of the 3-dimensional anatomy of teeth have been missing. Here, we evaluate the use of shortwave infrared radiation (SWIR) for navigation during stepwise access preparation. Nine teeth (3 anteriors, 3 premolars, and 3 molars) were explanted <i>en bloc</i> with intact periodontium including alveolar bone and mucosa from the upper or lower jaw of human body donors. Analysis was performed at baseline as well as at preparation depths of 5 mm, 7 mm, and 9 mm, respectively. For reflection, SWIR was used at a wavelength of 1,550 nm from the occlusal direction, whereas for transillumination, SWIR was passed through each sample at the marginal gingiva from the buccal as well as oral side at a wavelength of 1,300 nm. Pulpal structures could be identified as darker areas approximately 2 mm before reaching the pulp chamber using SWIR transillumination, although they were indistinguishable under normal circumstances. Furcation areas in molars appeared with higher intensity than areas with canals. The location of pulpal structures was confirmed by superimposition of segmented micro-computed tomography (µCT) images. By radiomic analysis, significant differences between pulpal and parapulpal areas could be detected in image features. With hierarchical cluster analysis, both segments could be confirmed and associated with specific clusters. The local thickness of µCTs was calculated and correlated with SWIR transillumination images, by which a linear dependency of thickness and intensity could be demonstrated. Lastly, by <i>in silico</i> simulations of light propagation, dentin tubules were shown to be a crucial factor for understanding the visibility of the pulp. In conclusion, SWIR transillumination may allow direct clinical live navigation during endodontic access preparation.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241262949"},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics. 牙周韧带细胞凋亡激活正畸中的 Lepr+ 骨生成器
Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241262706
H Liu, Y Zhang, Y Zhang, Y Huang, Y Yang, Y Zhao, S Chen, J Deng, W Li, B Han

Alveolar bone (AB) remodeling, including formation and absorption, is the foundation of orthodontic tooth movement (OTM). However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force-guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell-derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force-activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration.

牙槽骨(AB)重塑,包括形成和吸收,是正畸牙齿移动(OTM)的基础。然而,新骨形成的来源和机制仍不清楚。因此,我们以瘦素受体+(Lepr+)成骨细胞和牙周韧带细胞(PDLCs)为重点,旨在了解 OTM 期间骨形成的潜在机制。我们证明,在正畸骨再生过程中,由力诱导的 PDLC 细胞凋亡激活的 Lepr+ 细胞是一种独特的骨生成细胞。我们研究了体内和体外的骨形成。单细胞RNA测序分析和系谱追踪表明,Lepr代表了在OTM过程中被激活并分化成成骨细胞的干细胞亚群。在小鼠模型中靶向消融 Lepr+ 细胞会破坏正畸力引导的骨再生。此外,细胞凋亡和连续荧光标记实验显示,PDLCs 的凋亡先于新骨沉积。我们发现,PDL干细胞衍生的凋亡囊泡在体外激活了Lepr+细胞。抑制细胞凋亡后,正畸力激活的造骨细胞和成骨作用明显降低。值得注意的是,我们发现在 OTM 过程中,骨形成发生在受压侧;这在本文中是首次报道。总之,我们发现了 OTM 期间骨形成的潜在机制,这可能会为 AB 再生提供新的见解。
{"title":"Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics.","authors":"H Liu, Y Zhang, Y Zhang, Y Huang, Y Yang, Y Zhao, S Chen, J Deng, W Li, B Han","doi":"10.1177/00220345241262706","DOIUrl":"10.1177/00220345241262706","url":null,"abstract":"<p><p>Alveolar bone (AB) remodeling, including formation and absorption, is the foundation of orthodontic tooth movement (OTM). However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force-guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell-derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force-activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"937-947"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel Antimitotic Agent SP-1-39 Inhibits Head and Neck Squamous Cell Carcinoma. 新型抗溃疡剂 SP-1-39 抑制头颈部鳞状细胞癌
Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241261982
K L Adeleye, A R Li, Y Xie, S Pochampally, D Hamilton, F Garcia-Godoy, D D Miller, W Li

Effective management of head and neck cancer (HNC) poses a significant challenge in the field of oncology, due to its intricate pathophysiology and limited treatment options. The most common HNC malignancy is head and neck squamous cell carcinoma (HNSCC). HNSCC treatment includes a combination of surgery, radiation, and chemotherapy. While HNSCC is treatable if diagnosed early, this is often not the case and is considered incurable once in its late stages and metastatic disease has developed. Therapies are also limited once resistant disease has occurred. SP-1-39, a novel colchicine-binding site inhibitor (CBSI), has been recently reported for its potential efficacy in a variety of cancer cell lines including breast, melanoma, pancreatic, and prostate. SP-1-39 also shows abilities to overcome paclitaxel resistance in a paclitaxel-resistant prostate cancer xenograft model. To evaluate the potential of SP-1-39 as a new HNSCC treatment option, herein we systematically performed preclinical studies in HNSCC models using SP-1-39 and demonstrated that, in vitro, SP-1-39 inhibits the proliferation of 2 HNSCC cell lines with low nanomolar IC50 values (1.4 to 2.1 nM), induces HNSCC cell apoptosis in a dose-dependent manner, interferes with migration of HNSCC cells, and leads to HNSCC cell cycle arrest in the G2/M phase. In vivo, SP-1-39 suppresses the primary tumor growth of a Detroit 562 subcutaneous xenograft mouse model in 6- to 8-wk-old, male NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice, with no detectable cytotoxic effects at a low dose of 2.5 mg/kg. This efficacy of SP-1-39 is better when compared with the treatment using a reference chemotherapy drug, paclitaxel at 10 mg/kg. Collectively, these data demonstrate that SP-1-39 is a promising candidate for further development for more efficacious HNSCC treatment.

头颈癌(HNC)的病理生理学错综复杂,治疗方案有限,因此有效治疗头颈癌是肿瘤学领域的一项重大挑战。最常见的 HNC 恶性肿瘤是头颈部鳞状细胞癌(HNSCC)。HNSCC 的治疗包括手术、放疗和化疗。虽然 HNSCC 在早期诊断的情况下是可以治疗的,但情况往往并非如此,一旦进入晚期并出现转移性疾病,就会被认为是无法治愈的。一旦出现耐药性疾病,治疗方法也会受到限制。SP-1-39 是一种新型秋水仙碱结合位点抑制剂 (CBSI),最近有报道称它对乳腺癌、黑色素瘤、胰腺癌和前列腺癌等多种癌症细胞系具有潜在疗效。SP-1-39 还能在紫杉醇抗性前列腺癌异种移植模型中克服紫杉醇抗性。为了评估 SP-1-39 作为一种新的 HNSCC 治疗方案的潜力,我们在此使用 SP-1-39 对 HNSCC 模型进行了系统的临床前研究,结果表明,在体外,SP-1-39 能以较低的纳摩尔 IC50 值(1.4 至 2.1 nM)抑制 2 种 HNSCC 细胞株的增殖,以剂量依赖性方式诱导 HNSCC 细胞凋亡,干扰 HNSCC 细胞的迁移,并导致 HNSCC 细胞周期停滞在 G2/M 期。在体内,SP-1-39 可抑制 Detroit 562 皮下异种移植小鼠模型中 6 至 8 周大雄性 NSG(NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ)小鼠的原发性肿瘤生长,在 2.5 毫克/千克的低剂量下没有检测到细胞毒性作用。与使用参考化疗药物紫杉醇(10 毫克/千克)进行治疗相比,SP-1-39 的疗效更好。这些数据共同表明,SP-1-39 是一种有望进一步开发的候选药物,可用于更有效的 HNSCC 治疗。
{"title":"Novel Antimitotic Agent SP-1-39 Inhibits Head and Neck Squamous Cell Carcinoma.","authors":"K L Adeleye, A R Li, Y Xie, S Pochampally, D Hamilton, F Garcia-Godoy, D D Miller, W Li","doi":"10.1177/00220345241261982","DOIUrl":"10.1177/00220345241261982","url":null,"abstract":"<p><p>Effective management of head and neck cancer (HNC) poses a significant challenge in the field of oncology, due to its intricate pathophysiology and limited treatment options. The most common HNC malignancy is head and neck squamous cell carcinoma (HNSCC). HNSCC treatment includes a combination of surgery, radiation, and chemotherapy. While HNSCC is treatable if diagnosed early, this is often not the case and is considered incurable once in its late stages and metastatic disease has developed. Therapies are also limited once resistant disease has occurred. SP-1-39, a novel colchicine-binding site inhibitor (CBSI), has been recently reported for its potential efficacy in a variety of cancer cell lines including breast, melanoma, pancreatic, and prostate. SP-1-39 also shows abilities to overcome paclitaxel resistance in a paclitaxel-resistant prostate cancer xenograft model. To evaluate the potential of SP-1-39 as a new HNSCC treatment option, herein we systematically performed preclinical studies in HNSCC models using SP-1-39 and demonstrated that, in vitro, SP-1-39 inhibits the proliferation of 2 HNSCC cell lines with low nanomolar IC<sub>50</sub> values (1.4 to 2.1 nM), induces HNSCC cell apoptosis in a dose-dependent manner, interferes with migration of HNSCC cells, and leads to HNSCC cell cycle arrest in the G2/M phase. In vivo, SP-1-39 suppresses the primary tumor growth of a Detroit 562 subcutaneous xenograft mouse model in 6- to 8-wk-old, male NSG (NOD.Cg-Prkdc<sup>scid</sup> Il2rg<sup>tm1Wjl</sup>/SzJ) mice, with no detectable cytotoxic effects at a low dose of 2.5 mg/kg. This efficacy of SP-1-39 is better when compared with the treatment using a reference chemotherapy drug, paclitaxel at 10 mg/kg. Collectively, these data demonstrate that SP-1-39 is a promising candidate for further development for more efficacious HNSCC treatment.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"926-936"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Periodontitis and Diabetes Complications: A Danish Population-Based Study. 牙周炎与糖尿病并发症:一项基于丹麦人口的研究
Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241259954
F V Bitencourt, A Andersen, L Bjerg, A Sandbæk, H Li, G G Nascimento, R Spin-Neto, M A Peres, F R M Leite

Conflicting evidence suggests a link between diabetes-related microvascular complications and periodontitis. Reliable estimates have been hindered by small sample sizes and residual confounding. Moreover, the combined effects of microvascular complications and dyslipidemia on periodontitis have not been explored. Therefore, this study aimed to investigate the association between individual and combined diabetic microvascular complications (i.e., neuropathy and retinopathy) and moderate/severe periodontitis in a Danish population-based study. In addition, we assessed whether dyslipidemia modified these associations. This study comprised 15,922 participants with type 2 diabetes from the Health in Central Denmark study. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for individual and joint microvascular diabetes complications. The models adjusted for potential confounders, including sociodemographic factors, lifestyle behaviors, and health conditions. Inverse probability of treatment weighting (IPTW) balanced measured confounders between periodontitis and nonperiodontitis participants. Sensitivity analyses tested the findings' robustness by estimating E-values for unmeasured confounding and varying microvascular complication definitions. After IPTW, adjusted models revealed that diabetic neuropathy (OR 1.36, 95% CI 1.14 to 1.63) and retinopathy (OR 1.21, 95% CI 1.03 to 1.43) were significantly associated with moderate/severe periodontitis. Moreover, the coexistence of microvascular complications increased the odds 1.5-fold for moderate/severe periodontitis (OR 1.51, 95% CI 1.23 to 1.85). An effect modification of dyslipidemia on an additive scale was found, indicated by a positive relative excess risk due to interaction of 0.24 for neuropathy, 0.11 for retinopathy, and 0.44 for both complications. Sensitivity analysis ruled out unmeasured confounders and microvascular complication definitions as explanatory factors. Diabetic neuropathy and retinopathy, individually and combined, were associated with moderate/severe periodontitis. In addition, dyslipidemia had an additive positive effect modification on diabetic microvascular complications, elevating the odds of moderate/severe periodontitis. These findings may aid in identifying at-risk subgroups for diabetes-related microvascular complications and periodontitis, optimizing efforts to mitigate disease burden.

相互矛盾的证据表明,糖尿病相关微血管并发症与牙周炎之间存在联系。由于样本量小和残余混杂因素,可靠的估计结果受到阻碍。此外,尚未探讨微血管并发症和血脂异常对牙周炎的综合影响。因此,本研究旨在通过一项基于丹麦人群的研究,探讨糖尿病微血管并发症(即神经病变和视网膜病变)与中度/重度牙周炎之间的关联。此外,我们还评估了血脂异常是否会改变这些关联。这项研究包括丹麦中部健康研究中的 15,922 名 2 型糖尿病患者。我们采用多叉逻辑回归法估算了单个和联合微血管糖尿病并发症的几率比(OR)和 95% 置信区间(CI)。模型调整了潜在的混杂因素,包括社会人口因素、生活方式行为和健康状况。反向治疗概率加权(IPTW)平衡了牙周炎和非牙周炎参与者之间的测量混杂因素。敏感性分析通过估算未测量混杂因素的 E 值和不同的微血管并发症定义来检验研究结果的稳健性。IPTW调整后的模型显示,糖尿病神经病变(OR 1.36,95% CI 1.14-1.63)和视网膜病变(OR 1.21,95% CI 1.03-1.43)与中度/重度牙周炎显著相关。此外,同时存在微血管并发症会使中度/重度牙周炎的几率增加 1.5 倍(OR 1.51,95% CI 1.23 至 1.85)。研究还发现,血脂异常对并发症的影响具有叠加效应,神经病变、视网膜病变和两种并发症的交互作用导致的正向相对超额风险分别为 0.24、0.11 和 0.44。敏感性分析排除了作为解释因素的未测量混杂因素和微血管并发症定义。糖尿病神经病变和视网膜病变单独或合并与中度/重度牙周炎有关。此外,血脂异常对糖尿病微血管并发症也有叠加的积极影响,提高了中度/重度牙周炎的几率。这些发现有助于确定糖尿病相关微血管并发症和牙周炎的高危亚群,从而优化减轻疾病负担的工作。
{"title":"Periodontitis and Diabetes Complications: A Danish Population-Based Study.","authors":"F V Bitencourt, A Andersen, L Bjerg, A Sandbæk, H Li, G G Nascimento, R Spin-Neto, M A Peres, F R M Leite","doi":"10.1177/00220345241259954","DOIUrl":"10.1177/00220345241259954","url":null,"abstract":"<p><p>Conflicting evidence suggests a link between diabetes-related microvascular complications and periodontitis. Reliable estimates have been hindered by small sample sizes and residual confounding. Moreover, the combined effects of microvascular complications and dyslipidemia on periodontitis have not been explored. Therefore, this study aimed to investigate the association between individual and combined diabetic microvascular complications (i.e., neuropathy and retinopathy) and moderate/severe periodontitis in a Danish population-based study. In addition, we assessed whether dyslipidemia modified these associations. This study comprised 15,922 participants with type 2 diabetes from the Health in Central Denmark study. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for individual and joint microvascular diabetes complications. The models adjusted for potential confounders, including sociodemographic factors, lifestyle behaviors, and health conditions. Inverse probability of treatment weighting (IPTW) balanced measured confounders between periodontitis and nonperiodontitis participants. Sensitivity analyses tested the findings' robustness by estimating E-values for unmeasured confounding and varying microvascular complication definitions. After IPTW, adjusted models revealed that diabetic neuropathy (OR 1.36, 95% CI 1.14 to 1.63) and retinopathy (OR 1.21, 95% CI 1.03 to 1.43) were significantly associated with moderate/severe periodontitis. Moreover, the coexistence of microvascular complications increased the odds 1.5-fold for moderate/severe periodontitis (OR 1.51, 95% CI 1.23 to 1.85). An effect modification of dyslipidemia on an additive scale was found, indicated by a positive relative excess risk due to interaction of 0.24 for neuropathy, 0.11 for retinopathy, and 0.44 for both complications. Sensitivity analysis ruled out unmeasured confounders and microvascular complication definitions as explanatory factors. Diabetic neuropathy and retinopathy, individually and combined, were associated with moderate/severe periodontitis. In addition, dyslipidemia had an additive positive effect modification on diabetic microvascular complications, elevating the odds of moderate/severe periodontitis. These findings may aid in identifying at-risk subgroups for diabetes-related microvascular complications and periodontitis, optimizing efforts to mitigate disease burden.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"870-877"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PIEZO1 Promotes Odontoblast-Mediated Reactionary Dentinogenesis via SEMA3A. PIEZO1 通过 SEMA3A 促进牙本质母细胞介导的反应性牙本质生成
Pub Date : 2024-08-01 Epub Date: 2024-06-24 DOI: 10.1177/00220345241257866
P Huang, R X Jiang, F Wang, W W Qiao, Y T Ji, L Y Meng, Z Bian

Located at the interface of the dentin-pulp complex, the odontoblasts are specialized cells responsible for dentin synthesis and nociceptive signal detection in response to external stimuli. Recent studies have shown that the mechanosensitive ion channel PIEZO1 is involved in bone formation and remodeling through the influx of calcium ions, and it is abundantly expressed in odontoblasts. However, the specific role of PIEZO1 in reactionary dentinogenesis and the underlying mechanisms remain elusive. In this study, we found intense PIEZO1 expression in the plasma membrane and cytoplasm of odontoblasts in healthy human third molars, mouse mandibular molars, and human odontoblast-like cells (hOBLCs). In hOBLCs, PIEZO1 positively regulated DSPP, DMP1, and COL1A1 expression through the Ca2+/PI3K-Akt/SEMA3A signaling pathway. In addition, exogenous SEMA3A supplementation effectively reversed reduced mineralization capacity in PIEZO1-knockdown hOBLCs. In vivo, Piezo1 expression peaked at day 7 and returned to baseline at day 21 in a wild-type mice dentin injury model, with Sema3a presenting a similar expression pattern. To investigate the specific role of PIEZO1 in odontoblast-mediated reactionary dentinogenesis, mice with a conditional knockout of Piezo1 in odontoblasts were generated, and no significant differences in teeth phenotypes were observed between the control and conditional knockout (cKO) mice. Nevertheless, cKO mice exhibited reduced reactionary dentin formation and decreased Sema3a and Dsp positive staining after dentin injury, indicating impaired dental pulp repair by odontoblasts. In summary, these findings suggest that PIEZO1 enhances the mineralization capacity of hOBLCs in vitro via the Ca2+/PI3K-Akt/SEMA3A signaling pathway and contributes to reactionary dentinogenesis in vivo.

牙本质母细胞位于牙本质-牙髓复合体的界面,是负责牙本质合成和对外界刺激的痛觉信号检测的特化细胞。最近的研究表明,机械敏感性离子通道 PIEZO1 通过钙离子的流入参与骨形成和重塑,它在牙本质母细胞中大量表达。然而,PIEZO1 在反应性牙本质形成中的具体作用及其内在机制仍未确定。在这项研究中,我们发现 PIEZO1 在健康人类第三磨牙、小鼠下颌磨牙和人类牙本质母细胞样细胞(hOBLCs)的牙本质母细胞的质膜和细胞质中都有大量表达。在hOBLCs中,PIEZO1通过Ca2+/PI3K-Akt/SEMA3A信号通路正向调节DSPP、DMP1和COL1A1的表达。此外,补充外源 SEMA3A 能有效逆转 PIEZO1 敲除的 hOBLCs 矿化能力的降低。在体内,野生型小鼠牙本质损伤模型中,Piezo1的表达在第7天达到峰值,在第21天恢复到基线水平,Sema3a也呈现类似的表达模式。为了研究 PIEZO1 在牙本质母细胞介导的反应性牙本质生成中的特殊作用,我们在牙本质母细胞中产生了条件性敲除 Piezo1 的小鼠,在对照组和条件性敲除(cKO)小鼠之间没有观察到牙齿表型的显著差异。然而,cKO 小鼠的反应性牙本质形成减少,牙本质损伤后 Sema3a 和 Dsp 阳性染色减少,表明牙本质母细胞的牙髓修复功能受损。总之,这些研究结果表明,PIEZO1在体外通过Ca2+/PI3K-Akt/SEMA3A信号通路增强了hOBLCs的矿化能力,并有助于体内的反应性牙本质形成。
{"title":"PIEZO1 Promotes Odontoblast-Mediated Reactionary Dentinogenesis via SEMA3A.","authors":"P Huang, R X Jiang, F Wang, W W Qiao, Y T Ji, L Y Meng, Z Bian","doi":"10.1177/00220345241257866","DOIUrl":"10.1177/00220345241257866","url":null,"abstract":"<p><p>Located at the interface of the dentin-pulp complex, the odontoblasts are specialized cells responsible for dentin synthesis and nociceptive signal detection in response to external stimuli. Recent studies have shown that the mechanosensitive ion channel PIEZO1 is involved in bone formation and remodeling through the influx of calcium ions, and it is abundantly expressed in odontoblasts. However, the specific role of PIEZO1 in reactionary dentinogenesis and the underlying mechanisms remain elusive. In this study, we found intense PIEZO1 expression in the plasma membrane and cytoplasm of odontoblasts in healthy human third molars, mouse mandibular molars, and human odontoblast-like cells (hOBLCs). In hOBLCs, PIEZO1 positively regulated DSPP, DMP1, and COL1A1 expression through the Ca<sup>2+</sup>/PI3K-Akt/SEMA3A signaling pathway. In addition, exogenous SEMA3A supplementation effectively reversed reduced mineralization capacity in <i>PIEZO1</i>-knockdown hOBLCs. In vivo, Piezo1 expression peaked at day 7 and returned to baseline at day 21 in a wild-type mice dentin injury model, with Sema3a presenting a similar expression pattern. To investigate the specific role of PIEZO1 in odontoblast-mediated reactionary dentinogenesis, mice with a conditional knockout of <i>Piezo1</i> in odontoblasts were generated, and no significant differences in teeth phenotypes were observed between the control and conditional knockout (<i>cKO</i>) mice. Nevertheless, <i>cKO</i> mice exhibited reduced reactionary dentin formation and decreased Sema3a and Dsp positive staining after dentin injury, indicating impaired dental pulp repair by odontoblasts. In summary, these findings suggest that PIEZO1 enhances the mineralization capacity of hOBLCs in vitro via the Ca<sup>2+</sup>/PI3K-Akt/SEMA3A signaling pathway and contributes to reactionary dentinogenesis in vivo.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"889-898"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Use of Artificial Intelligence in Endodontics. 人工智能在牙髓病学中的应用。
Pub Date : 2024-08-01 Epub Date: 2024-05-31 DOI: 10.1177/00220345241255593
F C Setzer, J Li, A A Khan

Endodontics is the dental specialty foremost concerned with diseases of the pulp and periradicular tissues. Clinicians often face patients with varying symptoms, must critically assess radiographic images in 2 and 3 dimensions, derive complex diagnoses and decision making, and deliver sophisticated treatment. Paired with low intra- and interobserver agreement for radiographic interpretation and variations in treatment outcome resulting from nonstandardized clinical techniques, there exists an unmet need for support in the form of artificial intelligence (AI), providing automated biomedical image analysis, decision support, and assistance during treatment. In the past decade, there has been a steady increase in AI studies in endodontics but limited clinical application. This review focuses on critically assessing the recent advancements in endodontic AI research for clinical applications, including the detection and diagnosis of endodontic pathologies such as periapical lesions, fractures and resorptions, as well as clinical treatment outcome predictions. It discusses the benefits of AI-assisted diagnosis, treatment planning and execution, and future directions including augmented reality and robotics. It critically reviews the limitations and challenges imposed by the nature of endodontic data sets, AI transparency and generalization, and potential ethical dilemmas. In the near future, AI will significantly affect the everyday endodontic workflow, education, and continuous learning.

牙髓病学是牙科专业中最主要研究牙髓和根周组织疾病的学科。临床医生经常面对症状各异的患者,必须严格评估二维和三维放射影像,做出复杂的诊断和决策,并进行复杂的治疗。由于放射影像判读的观察者内部和观察者之间的一致性较低,以及非标准化临床技术导致的治疗效果差异,因此对人工智能(AI)形式的支持存在着尚未满足的需求,即在治疗过程中提供自动生物医学图像分析、决策支持和帮助。在过去十年中,人工智能在牙髓病学领域的研究稳步增加,但临床应用有限。这篇综述着重于批判性地评估牙髓病学人工智能研究在临床应用方面的最新进展,包括根尖周病变、骨折和吸收等牙髓病学病理的检测和诊断,以及临床治疗结果预测。报告讨论了人工智能辅助诊断、治疗规划和执行的优势,以及包括增强现实技术和机器人技术在内的未来发展方向。它批判性地回顾了牙髓病学数据集的性质、人工智能的透明度和通用性以及潜在的道德困境所带来的限制和挑战。在不久的将来,人工智能将极大地影响牙髓病学的日常工作流程、教育和持续学习。
{"title":"The Use of Artificial Intelligence in Endodontics.","authors":"F C Setzer, J Li, A A Khan","doi":"10.1177/00220345241255593","DOIUrl":"10.1177/00220345241255593","url":null,"abstract":"<p><p>Endodontics is the dental specialty foremost concerned with diseases of the pulp and periradicular tissues. Clinicians often face patients with varying symptoms, must critically assess radiographic images in 2 and 3 dimensions, derive complex diagnoses and decision making, and deliver sophisticated treatment. Paired with low intra- and interobserver agreement for radiographic interpretation and variations in treatment outcome resulting from nonstandardized clinical techniques, there exists an unmet need for support in the form of artificial intelligence (AI), providing automated biomedical image analysis, decision support, and assistance during treatment. In the past decade, there has been a steady increase in AI studies in endodontics but limited clinical application. This review focuses on critically assessing the recent advancements in endodontic AI research for clinical applications, including the detection and diagnosis of endodontic pathologies such as periapical lesions, fractures and resorptions, as well as clinical treatment outcome predictions. It discusses the benefits of AI-assisted diagnosis, treatment planning and execution, and future directions including augmented reality and robotics. It critically reviews the limitations and challenges imposed by the nature of endodontic data sets, AI transparency and generalization, and potential ethical dilemmas. In the near future, AI will significantly affect the everyday endodontic workflow, education, and continuous learning.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"853-862"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Changes in Use of Prenatal Dental Care After Brazil's Incentive Policy. 巴西实施激励政策后产前牙科保健使用情况的变化。
Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241258459
H S Schuch, M Furtado, A D P Chiavegatto Filho, H W Elani

In 2020, the Brazilian federal government launched the "Prevent Brazil" program to incentivize cities to improve their performance across 7 health care indicators, including prenatal dental care. Our study examines the impact of this policy on the use of oral health care among pregnant women in Brazil. We used a series of cross-sectional data from the Brazilian Public Health System from 2018 to 2023. We linked publicly available data from the Brazilian Ministry of Health and the Brazilian Institute of Geography and Statistics. Our outcome was the proportion of pregnant women receiving prenatal care who had at least 1 dental visit during the past year. Covariates included city-level socioeconomic (income and literacy), demographic (gender, race, and urban areas), and workforce variables (number of dentists working in the public health system per city/year). We estimated the impact of the policy on prenatal dental visits nationwide and stratified by geographic region using interrupted time-series analysis. Our analyses included 99.9% of all Brazilian cities (n = 5,562). The use of oral health care among pregnant women increased from 15% in 2018 to 69% in 2023. Adjusted estimates show that, after initiation of the Prevent Brazil, dental care use among pregnant women increased nationally at a rate of 4.6 percentage points per 4-mo period (95% confidence interval [CI] 4.5; 4.7). The policy's largest impact was in the North and Northeast regions, which have the lowest socioeconomic profiles (adjusted time-series rate 5.7 [95% CI 5.3; 6.1] and 5.2 [5.0; 5.4] percent points, respectively). Our findings support the positive impact of the Prevent Brazil policy on prenatal dental care in Brazil. The policy was associated with a countrywide improvement in prenatal dental care use, with a greater impact in socioeconomically disadvantaged regions.

2020 年,巴西联邦政府启动了 "预防巴西 "计划,激励各城市改善其在 7 项医疗保健指标方面的表现,其中包括产前牙科保健。我们的研究探讨了这一政策对巴西孕妇使用口腔保健的影响。我们使用了巴西公共卫生系统从 2018 年到 2023 年的一系列横截面数据。我们链接了巴西卫生部和巴西地理统计研究所的公开数据。我们的研究结果是接受产前检查的孕妇在过去一年中至少接受过一次牙科检查的比例。协变量包括城市一级的社会经济(收入和文化程度)、人口(性别、种族和城市地区)和劳动力变量(每个城市每年在公共卫生系统工作的牙医人数)。我们使用间断时间序列分析法估算了该政策对全国产前牙科就诊的影响,并按地理区域进行了分层。我们的分析包括 99.9% 的巴西城市(n = 5,562)。孕妇使用口腔保健的比例从 2018 年的 15%增至 2023 年的 69%。调整后的估计值显示,在巴西预防计划启动后,全国孕妇牙科保健使用率每 4 个月增加 4.6 个百分点(95% 置信区间 [CI] 4.5; 4.7)。该政策对社会经济地位最低的北部和东北部地区影响最大(调整后的时间序列比率分别为 5.7 [95% CI 5.3; 6.1] 和 5.2 [5.0; 5.4] 个百分点)。我们的研究结果支持 "预防巴西 "政策对巴西产前牙科保健的积极影响。该政策与全国范围内产前牙科保健使用率的提高有关,在社会经济条件较差的地区影响更大。
{"title":"Changes in Use of Prenatal Dental Care After Brazil's Incentive Policy.","authors":"H S Schuch, M Furtado, A D P Chiavegatto Filho, H W Elani","doi":"10.1177/00220345241258459","DOIUrl":"10.1177/00220345241258459","url":null,"abstract":"<p><p>In 2020, the Brazilian federal government launched the \"Prevent Brazil\" program to incentivize cities to improve their performance across 7 health care indicators, including prenatal dental care. Our study examines the impact of this policy on the use of oral health care among pregnant women in Brazil. We used a series of cross-sectional data from the Brazilian Public Health System from 2018 to 2023. We linked publicly available data from the Brazilian Ministry of Health and the Brazilian Institute of Geography and Statistics. Our outcome was the proportion of pregnant women receiving prenatal care who had at least 1 dental visit during the past year. Covariates included city-level socioeconomic (income and literacy), demographic (gender, race, and urban areas), and workforce variables (number of dentists working in the public health system per city/year). We estimated the impact of the policy on prenatal dental visits nationwide and stratified by geographic region using interrupted time-series analysis. Our analyses included 99.9% of all Brazilian cities (<i>n</i> = 5,562). The use of oral health care among pregnant women increased from 15% in 2018 to 69% in 2023. Adjusted estimates show that, after initiation of the Prevent Brazil, dental care use among pregnant women increased nationally at a rate of 4.6 percentage points per 4-mo period (95% confidence interval [CI] 4.5; 4.7). The policy's largest impact was in the North and Northeast regions, which have the lowest socioeconomic profiles (adjusted time-series rate 5.7 [95% CI 5.3; 6.1] and 5.2 [5.0; 5.4] percent points, respectively). Our findings support the positive impact of the Prevent Brazil policy on prenatal dental care in Brazil. The policy was associated with a countrywide improvement in prenatal dental care use, with a greater impact in socioeconomically disadvantaged regions.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"863-869"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of dental research
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1