Journal of Oral Biosciences最新文献_第3页

Proinflammatory cytokine-induced matrix metalloproteinase-9 expression in temporomandibular joint osteoarthritis is regulated by multiple intracellular mitogen-activated protein kinase pathways 促炎细胞因子诱导的基质金属蛋白酶-9在颞下颌关节骨性关节炎中的表达受多种细胞内丝裂原活化蛋白激酶途径的调控。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2025-01-02 DOI: 10.1016/j.job.2024.100609

Karen Abe , Seiji Yokota , Shikino Matsumoto , Hayato Ujiie , Emiko Kikuchi , Kazuro Satoh , Akira Ishisaki , Naoyuki Chosa

Objectives

Temporomandibular joint (TMJ) osteoarthritis (OA) is an inflammatory disease that involves periarthritis of the TMJ and destruction of cartilage tissue in the mandibular condyle. However, the role of proinflammatory cytokines in the expression levels of matrix metalloproteinase (MMP) remains inconclusive. Thus, in this study, we aimed to investigate the effect of proinflammatory cytokines on the expression of MMPs.

Methods

FLS1 cells (mouse TMJ-derived synovial cell line) were treated with tumor necrosis factor alpha (TNF-α) or interleukin (IL)-1β in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors. The mRNA expression levels of MMP-2 and MMP-9 were examined by reverse transcription-quantitative polymerase chain reaction. Additionally, the phosphorylation status of extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK in the FLS1 cells treated with TNF-α or IL-1β was evaluated by performing western blotting analysis.

Results

TNF-α and IL-1β significantly increased the expression of MMP-9 in the FLS1 cells; however, MMP-2 expression remained unaffected. Mitogen-activated protein kinase kinase (MEK) and p38 MAPK inhibitors significantly suppressed cytokine-induced MMP-9 upregulation. Conversely, Jun amino-terminal kinase (JNK) inhibitors further increased MMP-9 expression in the cells treated with TNF-α or IL-1β. Moreover, TNF-α and IL-1β enhanced ERK1/2 and p38 MAPK phosphorylation in the FLS1 cells.

Conclusions

TNF-α and IL-1β induced MMP-9 expression in the FLS1 cells via the MEK/ERK and p38 MAPK pathways and suppressed it via the JNK pathway. Thus, proinflammatory cytokines control MMP-9 expression in TMJ-OA by regulating multiple MAPK pathways.

目的：颞下颌关节（TMJ）骨关节炎（OA）是一种涉及颞下颌关节周炎和下颌髁软骨组织破坏的炎症性疾病。然而，促炎细胞因子在基质金属蛋白酶（MMP）表达水平中的作用尚不明确。因此，在本研究中，我们旨在探讨促炎细胞因子对MMPs表达的影响。方法：用肿瘤坏死因子α (TNF-α)或白细胞介素(IL)-1β处理FLS1细胞（小鼠tmj来源的滑膜细胞系），在有丝裂原活化蛋白激酶（MAPK）抑制剂存在或不存在的情况下。逆转录-定量聚合酶链反应检测MMP-2和MMP-9 mRNA表达水平。此外，通过western blotting分析TNF-α或IL-1β处理的FLS1细胞中细胞外信号调节激酶（ERK）1/2和p38 MAPK的磷酸化状态。结果：TNF-α和IL-1β显著提高了FLS1细胞中MMP-9的表达；然而，MMP-2的表达不受影响。丝裂原活化蛋白激酶（MEK）和p38 MAPK抑制剂显著抑制细胞因子诱导的MMP-9上调。相反，Jun氨基末端激酶（JNK）抑制剂在TNF-α或IL-1β处理的细胞中进一步增加MMP-9的表达。此外，TNF-α和IL-1β增强了FLS1细胞中ERK1/2和p38 MAPK的磷酸化。结论：TNF-α和IL-1β通过MEK/ERK和p38 MAPK通路诱导FLS1细胞中MMP-9的表达，并通过JNK通路抑制其表达。因此，促炎细胞因子通过调节多种MAPK通路控制TMJ-OA中MMP-9的表达。

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引用次数: 0

Possible role of superoxide dismutase 3 in hypoxia-induced developmental defects in murine molars 超氧化物歧化酶3在缺氧诱导的小鼠磨牙发育缺陷中的可能作用。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2025-01-01 DOI: 10.1016/j.job.2024.100611

Yeming Lu, Yukiho Kobayashi, Yuki Niki, Keiji Moriyama

Objectives

To investigate the effects of hypoxia on tooth germ development in mice and explore the underlying mechanisms.

Methods

Tooth germs were extracted from E14.5 mouse embryos and divided into the control and hypoxia groups for organ culture. The hypoxia group was exposed to hypoxia (0% oxygen) for 3 h, followed by normoxia for 21 h. After 2 or 7 days, samples were collected for morphometric analysis, reverse transcription-quantitative polymerase chain reaction, immunohistochemistry (IHC), and immunofluorescent staining (IF). Additionally, superoxide dismutase 3 (SOD3) expression patterns in mandibular molar tooth germs from C57BL/6 mouse embryos were analyzed using IHC. The SOD inhibitor sodium N, N-diethyldithiocarbamate trihydrate (DETC; 400 μM) was applied under normoxia for 3 days, followed by morphometry, IHC, and IF.

Results

After 7 days, the hypoxia group exhibited significantly smaller tooth size, fewer cusps, reduced cell proliferation, and increased apoptosis in the epithelium compared to the control group. Sod3 mRNA expression was higher than other Sod family member expressions in the control group. In the hypoxia group, Sod3 mRNA and SOD3 protein expression were significantly decreased, whereas hypoxia-inducible factor-1 expression and reactive oxygen species levels were increased. SOD3 was primarily expressed in the dental epithelium from E12.5 to E17.5. DETC impaired tooth germ development in the control group, resulting in a phenotype similar to that of the hypoxia group, and significantly reduced amelogenin and msh homeobox 2 expression in the epithelium.

Conclusions

Hypoxia impairs tooth germ development. SOD3 probably plays a protective role during this process.

目的：探讨缺氧对小鼠牙胚发育的影响及其机制。方法：从E14.5小鼠胚胎中提取牙胚，分为对照组和缺氧组进行器官培养。缺氧组小鼠缺氧（0%氧）3 h，再缺氧21 h。2 d或7 d后，采集标本进行形态计量学分析、逆转录-定量聚合酶链反应、免疫组化（IHC）和免疫荧光染色（IF）。此外，采用免疫组化方法分析了超氧化物歧化酶3 （SOD3）在C57BL/6小鼠下颌磨牙胚中的表达规律。SOD抑制剂N， N-二乙基二硫代氨基甲酸钠(DETC；400 μM)常温下处理3 d，然后进行形态测定、免疫组化和IF。结果：缺氧组与对照组相比，缺氧组牙齿尺寸明显减小，牙尖明显减少，细胞增殖减少，上皮细胞凋亡增加。对照组Sod3 mRNA表达高于其他Sod家族成员表达。缺氧组Sod3 mRNA和Sod3蛋白表达显著降低，缺氧诱导因子-1表达和活性氧水平升高。SOD3主要在E12.5 ~ E17.5牙上皮中表达。DETC损害了对照组的牙胚发育，导致与缺氧组相似的表型，并显著降低了上皮中amelogenin和msh homeobox 2的表达。结论：缺氧影响牙胚发育。SOD3可能在这一过程中起到保护作用。

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引用次数: 0

Characterization of the anti-Porphyromonas gingivalis compound in bilberry (Vaccinium myrtillus L.) and comparison with its analogs 越桔抗牙龈卟啉单胞菌化合物的鉴定及其与类似物的比较。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-12-31 DOI: 10.1016/j.job.2024.100610

Yutaroh Satoh , Kazuyuki Ishihara , Takaaki Kubota

Objectives

The bacterium Porphyromonas gingivalis is a major causative agent of periodontitis. In this study, the anti-P. gingivalis compound in bilberry (Vaccinium myrtillus L.) was identified and its activity was compared with that of its related analogs.

Methods

An acetone-soluble bilberry fruit extract was purified using silica gel column chromatography, and the minimum inhibitory concentrations (MICs) of the purified fractions were determined against P. gingivalis. After purification, mass spectrometry, nuclear magnetic resonance, and optical rotation analyses were performed to identify the anti-P. gingivalis compounds. Furthermore, cell assays were performed to assess the anti-P. gingivalis activity and cytotoxicity of the identified compounds. The activity of these compounds was compared with that of their pentacyclic triterpene analogs.

Results

The anti-P. gingivalis in bilberry extracts was identified as ursolic acid, a pentacyclic triterpene (PCT). The MIC of ursolic acid against P. gingivalis was between 6.25 and 12.5 μg/mL; it killed P. gingivalis within 4 h of treatment at these concentrations. However, it showed no cytotoxicity against gingival carcinoma Ca9-22 cells at the MIC. Ursane-type PCT, including ursolic acid and oleanane-type PCT, exhibited anti-P. gingivalis activity.

Conclusions

Ursolic acid found in bilberry fruit extract exhibits anti-P. gingivalis activity. Similar activity is observed in a class of PCTs with a common structure.

目的：牙龈卟啉单胞菌是引起牙周炎的主要病原体。在本研究中，anti-P。鉴定了越橘（Vaccinium myrtillus L.）中的gingivalis化合物，并与相关类似物进行了活性比较。方法：采用硅胶柱层析法纯化丙酮溶性越橘提取物，测定其对牙龈卟啉单胞菌的最低抑制浓度（mic）。纯化后进行质谱、核磁共振、旋光分析鉴定anti-P。gingivalis化合物。此外，进行细胞测定以评估抗p。所鉴定化合物的牙龈活性和细胞毒性。将这些化合物的活性与其五环三萜类似物进行了比较。结果：抗p；经鉴定，越桔提取物中的牙龈苷为熊果酸，是一种五环三萜（PCT）。熊果酸对牙龈卟啉单胞菌的MIC在6.25 ~ 12.5 μg/mL之间；在这些浓度下，它在4小时内杀死牙龈假单胞菌。然而，在MIC下，它对牙龈癌Ca9-22细胞没有细胞毒性。熊果酸型PCT和齐墩烷型PCT均具有抗p活性。gingivalis活动。结论：越橘果提取物中熊果酸具有抗磷活性。gingivalis活动。在一类具有共同结构的pct中观察到类似的活性。

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引用次数: 0

Profiling of the microbes on the surface of smartphone touchscreens 智能手机触摸屏表面微生物的分析。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-12-30 DOI: 10.1016/j.job.2024.100607

Nanase Takahashi , Anna Wakui , Yume Sekizawa , Miho Kawachi , Mirai Sekiguchi , Takashi Abe , Aya Sato , Misato Miyazawa , Manami Imai , Nagara Kaku , Shingo Maruyama , Hiroto Sano , Nahoko Kakihara , Jumpei Washio , Yuki Abiko , Kaori Tanaka , Nobuhiro Takahashi , Takuichi Sato

The commensal microbiota of the finger-skin before and after ethanol disinfection were characterized and compared with the microbes isolated from the surface of smartphone touchscreens. The number of bacteria on the smartphone touchscreens was low, similar to that on the fingers after ethanol disinfection, suggesting that the surface of the touchscreens may not be suitable for the growth of microorganisms, rather than the surface of the fingers. Furthermore, ethanol disinfection reduced the number of bacteria on the finger-skin to 1/13 of the original count before disinfection.

对乙醇消毒前后手指皮肤的共生菌群进行了表征，并与智能手机触摸屏表面分离的微生物进行了比较。智能手机触摸屏上的细菌数量较低，与乙醇消毒后的手指上的细菌数量相似，这表明触摸屏表面可能不适合微生物生长，而不是手指表面。此外，乙醇消毒将手指皮肤上的细菌数量减少到消毒前的1/13。

引用次数: 0

Tooth loss-associated neuroplasticity of mastication-related motor cortical neurons 咀嚼相关运动皮质神经元与牙齿脱落相关的神经可塑性。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-12-28 DOI: 10.1016/j.job.2024.100606

Takafumi Katagiri , Shiro Nakamura , Yoshihisa Tachibana , Kiyomi Nakayama , Ayako Mochizuki , Masanori Dantsuji , Kazuyoshi Baba , Tomio Inoue

Objectives

The cerebral cortex contains neurons that play a pivotal role in controlling rhythmic masticatory jaw movements. However, the population characteristics of individual cortical neuronal activity during mastication and the impact of tooth loss on these characteristics remain unclear. Thus, in this study, we aimed to determine the activity patterns of mastication-related motor cortical neurons elicited during mastication and examine the effects of tooth extraction on neuronal activity using two-photon Ca²⁺ imaging in head-restrained awake mice.

Methods

GCaMP6f-expressing adeno-associated virus serotype 1 was injected into the left motor cortex (centered 2 mm anterior and 2 mm lateral to the bregma) and electromyography (EMG) electrodes were implanted into the right masseter and digastric muscles of 6–8-week-old C57BL/6j mice. Three weeks after surgery, in vivo two-photon Ca²⁺ imaging of layer (L) 2/3 neurons and simultaneous EMG recordings were performed during the masticatory sequence.

Results

Mastication induced a remarkable increase in the power and frequency of Ca²⁺ responses and correlated with majority of the mastication-related motor cortical L2/3 neuronal activity. These mastication-related changes correlated with the activity of neurons with low baseline activity that occurred before mastication. Extraction of the right upper three molars caused clear neuroplastic changes in the mastication-induced Ca²⁺ activity of L2/3 neurons.

Conclusions

Our in vivo imaging study provides new insights into the neuronal basis of tooth loss-induced cortical neuroplasticity, and suggests a possible therapeutic approach for oral sensorimotor dysfunction.

目的：大脑皮层包含的神经元在控制有节奏的咀嚼颚运动中起关键作用。然而，咀嚼过程中个体皮质神经元活动的群体特征以及牙齿脱落对这些特征的影响尚不清楚。因此，在这项研究中，我们的目的是确定咀嚼过程中引发的咀嚼相关运动皮质神经元的活动模式，并利用双光子Ca2+成像检查拔牙对头部受限清醒小鼠神经元活动的影响。方法：将表达gcamp6f的1型腺相关病毒注射到6-8周龄C57BL/6j小鼠的左侧运动皮层（位于脑前侧2 mm和2 mm），并在右侧咬肌和二腹肌植入肌电电极。手术后三周，在咀嚼序列中进行层(L) 2/3神经元的体内双光子Ca2+成像和同时肌电图记录。结果：咀嚼诱导Ca2+反应的强度和频率显著增加，并与咀嚼相关的大多数运动皮质L2/3神经元活动相关。这些咀嚼相关的变化与咀嚼前发生的低基线活动神经元的活动相关。拔除右上三颗磨牙后，咀嚼诱导的L2/3神经元Ca2+活性发生明显的神经可塑性变化。结论：我们的体内成像研究为牙齿脱落引起的皮质神经可塑性的神经元基础提供了新的见解，并为口腔感觉运动功能障碍的治疗提供了可能的方法。

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引用次数: 0

Sex determination method using the third cervical vertebral body by head and neck CT 第三颈椎椎体通过头颈部CT确定性别的方法。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-12-27 DOI: 10.1016/j.job.2024.100608

Akihiro Ochiai , Atsushi Iwawaki , Yusei Otaka , Takeru Ishii , Kota Ozawa , Yuko Otomo , Shinji Kito , Hideki Saka

Objectives

This study aimed to measure the volume of the third cervical vertebra using head and neck multi-detector computed tomography (MDCT) and establish a sex determination model based on sex differences in volume.

Methods

Head and neck CT images of 85 patients were obtained for dental diagnostic and therapeutic purposes. Digital Imaging and Communications in Medicine (DICOM) data obtained from head and neck CT were constructed using a three-dimensional image analysis software. A region of interest was created that included the entire third cervical vertebra and its volume was measured. Descriptive statistics were calculated for the measurements, and the means, standard deviations, and medians of the measurements were calculated separately for men and women. To create a sex determination model, binomial logistic regression analysis was performed using the training data group, with vertebral volume and sex as the explanatory and objective variables, respectively.

Results

The mean score of men was significantly higher than that of women. The sex determination model using the volume of the third cervical vertebral body resulted in an 80% correct sex classification rate.

Conclusion

The sex determination model can be used with other regional methods to aid sex determination.

目的：本研究旨在利用头颈部多探测器计算机断层扫描（MDCT）测量第三颈椎体积，并建立基于体积性别差异的性别判定模型。方法：对85例患者的头颈部CT图像进行临床诊断和治疗。使用三维图像分析软件构建头颈部CT的医学数字成像与通信（DICOM）数据。创建了一个包括整个第三颈椎的感兴趣区域，并测量了其体积。对测量结果进行描述性统计，并分别计算男性和女性测量结果的平均值、标准差和中位数。为了建立性别决定模型，使用训练数据组进行二项逻辑回归分析，分别以椎体体积和性别作为解释变量和客观变量。结果：男性的平均得分明显高于女性。使用第三颈椎体积的性别决定模型的性别分类正确率为80%。结论：该性别决定模型可与其他区域性方法一起辅助性别决定。

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引用次数: 0

Prrx2, the paired-related homeobox transcription factor, functions as a potential regulator of pannexin 3 expression in odontoblast differentiation 配对相关的同源盒转录因子Prrx2在成牙细胞分化过程中可能调控pannexin 3的表达。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-12-27 DOI: 10.1016/j.job.2024.100601

Manami Tanaka , Asuna Sugimoto , Kokoro Iwata , Yumiko Nakashima , Muhammad Dhiaulfikri Nauval Hadiana , Yusuke Iwabuchi , Kanae Wada , Atsushi Oishi , Tsutomu Iwamoto

Objectives

This study aimed to elucidate the roles of Prrx1 and Prrx2, homeobox transcription factors, in tooth development and determine whether Prrx2 regulates pannexin 3 (Panx3) expression, which is important in preodontoblasts.

Methods

Tooth sections were prepared from 13.5-, 15.5-, and 18.5-day-old embryonic ICR mice, and Prrx1- and Prrx2-expressing cells were identified by in situ hybridization. To clarify the direct relationship between Prrx2 and Panx3, dual-luciferase reporter assay and electrophoretic mobility shift assay (EMSA) were performed. The effect of endogenous Prrx2 suppression on Panx3 expression was analyzed using an siRNA assay.

Results

In situ hybridization revealed that in the molars, Prrx1 and Prrx2 were similarly expressed in the bud and cap stages; however, only Prrx2 was expressed in preodontoblasts at the bell stage. In the incisors, Prrx2-expressing cells were observed from dental papilla cells to preodontoblasts. In serial sections, Prrx2-expressing cells in preodontoblasts corresponded to Panx3-expressing cells. Luciferase reporter assay using luciferase reporter plasmids containing Panx3 promoter revealed that Prrx2 overexpression in HEK293 cells significantly increased luciferase activity. EMSA of nuclear extract proteins from Prrx2-overexpressing HEK293 cells or mouse dental papilla-derived cells to the Panx3 promoter showed the protein-probe complex bands. SiRNA assay revealed that Prrx2 knockdown inhibited Panx3 expression.

Conclusions

Our results suggest that Prrx2 may regulate Panx3 expression during odontoblastic differentiation.

目的：本研究旨在阐明同源盒转录因子Prrx1和Prrx2在牙齿发育中的作用，并确定Prrx2是否调控pannexin 3 （Panx3）的表达，pannexin 3在成牙前细胞中起重要作用。方法：分别取13.5、15.5、18.5日龄ICR小鼠胚牙切片，原位杂交鉴定表达Prrx1和prrx2的细胞。为了明确Prrx2和Panx3之间的直接关系，我们进行了双荧光素酶报告基因实验和电泳迁移量转移实验（EMSA）。采用siRNA法分析内源性Prrx2抑制对Panx3表达的影响。结果：原位杂交结果显示，Prrx1和Prrx2在臼齿的芽和帽期表达相似；而在钟形期，只有Prrx2在成牙胚中表达。在门牙中，从牙乳头细胞到成牙前细胞均有表达prrx2的细胞。在连续切片中，原成牙细胞中表达prrx2的细胞与表达panx3的细胞相对应。利用含有Panx3启动子的荧光素酶报告质粒进行荧光素酶报告基因检测发现，在HEK293细胞中过表达Prrx2可显著提高荧光素酶活性。过表达prrx2的HEK293细胞或小鼠牙乳头源性细胞的核提取物蛋白对Panx3启动子的EMSA显示蛋白探针复合物带。SiRNA分析显示，Prrx2敲低抑制了Panx3的表达。结论：Prrx2可能在成牙细胞分化过程中调控Panx3的表达。

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引用次数: 0

Gene expression profiles in human dental pulp stem cells treated short-term with lipopolysaccharides before and after osteoinduction 骨诱导前后短时间脂多糖处理人牙髓干细胞的基因表达谱。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-12-20 DOI: 10.1016/j.job.2024.100603

Ai Orimoto , Ziyi Wang , Mitsuaki Ono , Chiaki Kitamura , Kentaro Ono

Objectives

Dental pulp stem cells (DPSCs) are essential for reparative dentinogenesis following damage or infection. DPSCs surrounding theblood vessels in the central region of the dental pulp actively proliferate after tooth injury and differentiate into new odontoblast-like cells or odontoblasts to form reparative dentin. However, the signaling pathways involved in undifferentiated and osteodifferentiated DPSCs under inflammatory conditions remain unclear. This study aimed to compare the expression profiles of immortalized undifferentiated and osteo-differentiated human DPSCs (hDPSCs) treated with and without lipopolysaccharide (LPS) to elucidate the molecular regulatory mechanisms involved in inflammatory conditions.

Methods

We investigated the differences between undifferentiated and osteodifferentiated hDPSCs in response to LPS. RNA-seq analyses of undifferentiated and osteodifferentiated hDPSCs were performed with and without LPS.

Results

Whole-transcriptome profiling revealed distinct differences in the expression patterns of LPS-treated undifferentiated and osteodifferentiated DPSCs. Death-associated protein kinase 1 levels downregulated in LPS-treated osteodifferentiated cells, inhibiting apoptosis and enhancing cell survival After LPS treatment, osteodifferentiated DPSCs exhibited higher expression levels of various inflammatory cytokines and chemokines than undifferentiated DPSCs.

Conclusion

This study provides valuable transcriptomic data as a critical resource for uncovering potential therapeutic targets to enhance cell survival and regulate inflammation within the dental pulp. By elucidating the key molecular mechanisms and identifying specific gene expression changes linked to inflammatory and immune responses, these findings provide significant insights into osteo-differentiated hDPSCs.

目的：牙髓干细胞（DPSCs）在牙本质损伤或感染后的修复性牙本质形成中是必不可少的。牙髓中心血管周围的DPSCs在牙齿损伤后积极增殖，分化为新的成牙细胞样细胞或成牙细胞，形成修复性牙本质。然而，炎症条件下未分化和骨分化DPSCs的信号通路尚不清楚。本研究旨在比较永生化未分化和骨分化的人DPSCs （hdpsc）在脂多糖（LPS）和未脂多糖（LPS）处理下的表达谱，以阐明参与炎症条件的分子调控机制。方法：研究未分化和骨分化的hdpsc在LPS作用下的差异。使用LPS和不使用LPS对未分化和骨分化的hdpsc进行RNA-seq分析。结果：全转录组分析显示，lps处理的未分化和骨分化DPSCs的表达模式存在明显差异。在lps处理的骨分化细胞中，死亡相关蛋白激酶1水平下调，抑制细胞凋亡，提高细胞存活率。LPS处理后，骨分化的DPSCs比未分化的DPSCs表现出更高的各种炎症细胞因子和趋化因子的表达水平。结论：本研究提供了有价值的转录组学数据，为发现潜在的治疗靶点以提高牙髓细胞存活率和调节牙髓内炎症提供了重要资源。通过阐明关键的分子机制和识别与炎症和免疫反应相关的特定基因表达变化，这些发现为骨分化的hdpsc提供了重要的见解。

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引用次数: 0

The potential role of chromodomain helicase DNA-binding protein 3 in defining the cervical width by regulating the early growth stage of the apical papilla during tooth development 染色体结构域解旋酶dna结合蛋白3在牙齿发育过程中通过调节尖乳头的早期生长阶段来确定颈宽度的潜在作用。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-12-20 DOI: 10.1016/j.job.2024.100604

Kento Shimamura , Toshiki Nojiri , Hisatomo Kondo , Yunosuke Ikeda , Rika Yasuhara , Hiroko Ida-Yonemochi , Keishi Otsu , Hidemitsu Harada , Kenji Mishima , Hayato Ohshima , Takuya Kobayashi , Tarou Irié

Objective

This study aimed to evaluate the role of the chromodomain helicase DNA-binding protein 3 (CHD3) in tooth morphogenesis in Chd3 knockout mice.

Methods

Chd3 knockout mice were generated using the CRISPR-Cas9 method. Mandibular first molars were extracted from the mice and their littermates and morphometrically analyzed. Subsequent histological and immunohistochemical analyses of teeth were performed at each developmental stage. Chd3 knockdown in mesenchymal cells from the dental papilla (mDP) and Hertwig's epithelial root sheath (HERS) was performed by Chd3 shRNA transduction or a control using an adenoviral vector. These effects were examined using cell proliferation assays and quantitative real-time polymerase chain reaction.

Results

Narrowing of tooth cervical width was observed in mandibular first molars of Chd3 knockout mice. On postnatal day (PN) 8, the cervical width was narrow before root formation in tooth germs. The number of Ki-67-positive cells decreased in the dental mesenchyme at PN1 and apical papilla at PN8. Chd3 promoted the proliferation of dental mesenchymal cells, but no significant changes were observed in HERS epithelial cells. Chd3 maintained sonic hedgehog (Shh) expression and inhibited that of bone morphogenetic protein (Bmp)4 in dental mesenchymal cells, maintaining Shh and Wnt3a expression and inhibited that of Bmp2 in HERS epithelial cells.

Conclusion

Chd3 may regulate tooth cervical width during the early growth stage of the apical papilla via Shh, Bmp, and Wnt signaling.

目的：探讨染色体结构域解旋酶dna结合蛋白3 （CHD3）在CHD3基因敲除小鼠牙齿形态发生中的作用。方法：采用CRISPR-Cas9方法构建Chd3基因敲除小鼠。从小鼠及其窝仔身上提取下颌第一磨牙并进行形态计量学分析。随后在每个发育阶段对牙齿进行组织学和免疫组织化学分析。在牙乳头（mDP）和Hertwig上皮根鞘（HERS）的间充质细胞中，通过Chd3 shRNA转导或使用腺病毒载体进行对照，实现Chd3的下调。使用细胞增殖试验和定量实时聚合酶链反应检测这些影响。结果：Chd3基因敲除小鼠下颌第一磨牙牙颈宽度变窄。出生后第8天（PN），牙胚根形成前颈宽较窄。PN1牙间质和PN8牙顶乳头中ki -67阳性细胞数量减少。Chd3对牙间充质细胞增殖有促进作用，但对HERS上皮细胞无明显影响。Chd3在牙间质细胞中维持sonic hedgehog （Shh）的表达，抑制骨形态发生蛋白（Bmp）4的表达，维持Shh和Wnt3a的表达，抑制HERS上皮细胞中Bmp2的表达。结论：Chd3可能通过Shh、Bmp和Wnt信号调控牙颈宽度。

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引用次数: 0

Low-molecular-weight polyphenol promotes cell sensitivity to cisplatin and alleviates cancer-related muscle atrophy via NF-κB suppression in oral squamous cell carcinoma 低分子多酚促进细胞对顺铂的敏感性，并通过抑制NF-κB减轻口腔鳞状细胞癌的癌相关性肌肉萎缩。

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences

Pub Date : 2024-12-19 DOI: 10.1016/j.job.2024.100595

Yun-Ching Chang , Yu-Yan Lan , Hung-Yu Lin , Cheng Liu , Sue-Joan Chang

Objective

Drug resistance and subsequent adverse effects, such as cancer cachexia, limit the clinical use of cisplatin. Oligonol® (Olg), a low-molecular-weight polyphenol, exhibits NF-κB inhibitory properties. NF-κB activation has been implicated in cisplatin resistance of cancer cells and skeletal muscle wasting. Therefore, we hypothesized that combined cisplatin and Olg could overcome chemoresistance and reduce muscle atrophy.

Methods

To investigate the efficiency of Olg, oral squamous cell carcinoma (OSCC) cells were used for chemosensitivity, and human skeletal muscle myoblast (HSkMC) was used for muscle atrophy. HSkMCs treated with OSCC cell-derived conditioned medium were used to examine the role of Olg in muscle atrophy mediated by the tumor inflammatory microenvironment.

Results

Olg exerted little effect on the viability of OSCC cells by promoting apoptotic cell death. However, it exhibited excellent capability to enhance the sensitivity of OSCC cells to cisplatin and overcome the acquired cisplatin resistance of OSCC. We revealed that NF-κB signaling contributes to cisplatin resistance in OSCC cells, whereas Olg enhances cell sensitivity to cisplatin by NF-κB suppression. Conversely, Olg contributes to a positive protein turnover and alleviates cisplatin-induced muscle atrophy by regulating Akt/mTOR/p70S6K and NF-κB/MuRF1 pathway. Olg represses TNF-α and interleukin 6 driven from OSCC cells and alleviates muscle atrophy mediated by the tumor inflammatory microenvironment.

Conclusions

Olg enhanced cisplatin chemosensitivity and reduced its adverse effects on skeletal muscle, suggesting its potential as a chemosensitizing agent for cisplatin. Further animal and clinical studies are required to validate these findings.

目的：耐药及继发的恶性恶病质等不良反应限制了顺铂的临床应用。Oligonol®（Olg）是一种低分子量多酚，具有抑制NF-κB的特性。NF-κB活化与癌细胞的顺铂耐药和骨骼肌萎缩有关。因此，我们假设顺铂联合Olg可以克服化疗耐药，减少肌肉萎缩。方法：以口腔鳞状细胞癌（OSCC）细胞为化学敏感性，人骨骼肌成肌细胞（HSkMC）为肌肉萎缩细胞，研究Olg的作用。用OSCC细胞衍生的条件培养基处理HSkMCs，研究Olg在肿瘤炎症微环境介导的肌肉萎缩中的作用。结果：Olg通过促进凋亡细胞的死亡，对OSCC细胞的生存能力影响不大。然而，它在提高OSCC细胞对顺铂的敏感性和克服OSCC获得性顺铂耐药方面表现出优异的能力。我们发现NF-κB信号传导有助于OSCC细胞对顺铂的耐药，而Olg通过抑制NF-κB增强细胞对顺铂的敏感性。相反，Olg通过调节Akt/mTOR/p70S6K和NF-κB/MuRF1通路，促进正向蛋白转换，缓解顺铂诱导的肌肉萎缩。Olg抑制OSCC细胞驱动的TNF-α和白细胞介素6，减轻肿瘤炎症微环境介导的肌肉萎缩。结论：Olg增强顺铂化疗敏感性，减少其对骨骼肌的不良反应，提示其作为顺铂化疗增敏剂的潜力。需要进一步的动物和临床研究来验证这些发现。

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