International Journal of Oral Science最新文献_第3页

METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs METTL7A 介导的 corin m6A 修饰可逆转双膦酸盐对口面部 BMSC 骨细胞成骨分化的影响

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-23 DOI: 10.1038/s41368-024-00303-1

Yizhou Jin, Xiao Han, Yuejun Wang, Zhipeng Fan

{"title":"METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs","authors":"Yizhou Jin, Xiao Han, Yuejun Wang, Zhipeng Fan","doi":"10.1038/s41368-024-00303-1","DOIUrl":"https://doi.org/10.1038/s41368-024-00303-1","url":null,"abstract":"Bisphosphonate-related osteonecrosis of jaw (BRONJ) is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells (BMSCs). Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders. However, the role of corin in BRONJ-related BMSCs dysfunction remains unclarified. A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation. Corin knockdown inhibits BMSCs osteogenic differentiation, whereas corin overexpression or soluble corin (sCorin) exerts a promotion effect. Furthermore, corin expression is negatively regulated by bisphosphonates (BPs). Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability. Mechanistically, we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation. PD98059 (a selective ERK inhibitor) blocks the corin-mediated promotion effect. With regard to the high methylation level of corin during osteogenic differentiation, we apply a non-selective m6A methylase inhibitor, Cycloleucine, which also blocks the corin-mediated promotion effect. Furthermore, we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function, indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability. To conclude, our study reveals that corin reverses BPs-induced BMSCs dysfunction, and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway. We hope this brings new insights into future clinical treatments for BRONJ.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure 多组学分析显示，VDR 是间充质干细胞衰老的核心调节因子，已知与高脂饮食暴露后的骨质疏松症有关

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-22 DOI: 10.1038/s41368-024-00309-9

Jiayao Chen, Shuhong Kuang, Jietao Cen, Yong Zhang, Zongshan Shen, Wei Qin, Qiting Huang, Zifeng Wang, Xianling Gao, Fang Huang, Zhengmei Lin

{"title":"Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure","authors":"Jiayao Chen, Shuhong Kuang, Jietao Cen, Yong Zhang, Zongshan Shen, Wei Qin, Qiting Huang, Zifeng Wang, Xianling Gao, Fang Huang, Zhengmei Lin","doi":"10.1038/s41368-024-00309-9","DOIUrl":"https://doi.org/10.1038/s41368-024-00309-9","url":null,"abstract":"The consumption of a high-fat diet (HFD) has been linked to osteoporosis and an increased risk of fragility fractures. However, the specific mechanisms of HFD-induced osteoporosis are not fully understood. Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells (BMSCs), diminishing their proliferation and osteogenic capability, and thereby contributes to osteoporosis. Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor (VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice, suggesting that VDR is a key regulator of BMSC senescence. Notably, the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis, bone mass, and other bone parameters. Mechanistically, VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species (ROS) levels and preserving mitochondrial function. Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2 (SOD2)-ROS axis.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer’s disease 人牙髓干细胞通过 AKT-GSK3β-Nrf2 通路减轻阿尔茨海默病的神经病理变化和认知能力下降

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-13 DOI: 10.1038/s41368-024-00300-4

Wei Xiong, Ye Liu, Heng Zhou, Junyi Li, Shuili Jing, Cailei Jiang, Mei Li, Yan He, Qingsong Ye

{"title":"Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer’s disease","authors":"Wei Xiong, Ye Liu, Heng Zhou, Junyi Li, Shuili Jing, Cailei Jiang, Mei Li, Yan He, Qingsong Ye","doi":"10.1038/s41368-024-00300-4","DOIUrl":"https://doi.org/10.1038/s41368-024-00300-4","url":null,"abstract":"Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer’s disease (AD), particularly in the early stages of the disease. The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases. We herein demonstrated that human dental pulp stem cells (hDPSCs) mediated oxidative stress improvement and neuroreparative effects in in vitro AD models, playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons. Importantly, these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs, with the treated mice showing significant improvement in cognitive function and neuropathological features. Mechanistically, antioxidant and neuroprotective effects, as well as cognitive enhancements elicited by hDPSCs, were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway. In conclusion, our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models, which may be a tremendous potential therapeutic candidate for Alzheimer’s disease.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140914955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the oral-gut connection: chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE−/− Mice on a high-fat diet 揭开口腔与肠道的联系：慢性根尖牙周炎通过肠道微生物群失调和代谢物改变加速高脂饮食载脂蛋白E-/-小鼠的动脉粥样硬化

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-13 DOI: 10.1038/s41368-024-00301-3

Guowu Gan, Shihan Lin, Yufang Luo, Yu Zeng, Beibei Lu, Ren Zhang, Shuai Chen, Huaxiang Lei, Zhiyu Cai, Xiaojing Huang

{"title":"Unveiling the oral-gut connection: chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE−/− Mice on a high-fat diet","authors":"Guowu Gan, Shihan Lin, Yufang Luo, Yu Zeng, Beibei Lu, Ren Zhang, Shuai Chen, Huaxiang Lei, Zhiyu Cai, Xiaojing Huang","doi":"10.1038/s41368-024-00301-3","DOIUrl":"https://doi.org/10.1038/s41368-024-00301-3","url":null,"abstract":"The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE−/− mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE−/− mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140914976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sinensetin protects against periodontitis through binding to Bach1 enhancing its ubiquitination degradation and improving oxidative stress Sinensetin 通过与 Bach1 结合，增强其泛素化降解并改善氧化应激，从而预防牙周炎

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-11 DOI: 10.1038/s41368-024-00305-z

Zhiyao Yuan, Junjie Li, Fuyu Xiao, Yu Wu, Zhiting Zhang, Jiahong Shi, Jun Qian, Xudong Wu, Fuhua Yan

{"title":"Sinensetin protects against periodontitis through binding to Bach1 enhancing its ubiquitination degradation and improving oxidative stress","authors":"Zhiyao Yuan, Junjie Li, Fuyu Xiao, Yu Wu, Zhiting Zhang, Jiahong Shi, Jun Qian, Xudong Wu, Fuhua Yan","doi":"10.1038/s41368-024-00305-z","DOIUrl":"https://doi.org/10.1038/s41368-024-00305-z","url":null,"abstract":"Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A 3D In-vitro model of the human dentine interface shows long-range osteoinduction from the dentine surface 人体牙本质界面的三维体外模型显示了牙本质表面的长程骨诱导作用

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-11 DOI: 10.1038/s41368-024-00298-9

William Macalester, Asme Boussahel, Rafael O. Moreno-Tortolero, Mark R. Shannon, Nicola West, Darryl Hill, Adam Perriman

{"title":"A 3D In-vitro model of the human dentine interface shows long-range osteoinduction from the dentine surface","authors":"William Macalester, Asme Boussahel, Rafael O. Moreno-Tortolero, Mark R. Shannon, Nicola West, Darryl Hill, Adam Perriman","doi":"10.1038/s41368-024-00298-9","DOIUrl":"https://doi.org/10.1038/s41368-024-00298-9","url":null,"abstract":"Emerging regenerative cell therapies for alveolar bone loss have begun to explore the use of cell laden hydrogels for minimally invasive surgery to treat small and spatially complex maxilla-oral defects. However, the oral cavity presents a unique and challenging environment for in vivo bone tissue engineering, exhibiting both hard and soft periodontal tissue as well as acting as key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems, which will impact on cell fate and subsequent treatment efficacy. Herein, we design and bioprint a facile 3D in vitro model of a human dentine interface to probe the effect of the dentine surface on human mesenchymal stem cells (hMSCs) encapsulated in a microporous hydrogel bioink. We demonstrate that the dentine substrate induces osteogenic differentiation of encapsulated hMSCs, and that both dentine and β-tricalcium phosphate substrates stimulate extracellular matrix production and maturation at the gel-media interface, which is distal to the gel-substrate interface. Our findings demonstrate the potential for long-range effects on stem cells by mineralized surfaces during bone tissue engineering and provide a framework for the rapid development of 3D dentine-bone interface models.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling 抑制 m1A 可通过下调 MYC/PD-L1 信号促进溶瘤病毒诱导的抗肿瘤免疫力

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-10 DOI: 10.1038/s41368-024-00304-0

Shujin Li, Tian Feng, Yuantong Liu, Qichao Yang, An Song, Shuo Wang, Jun Xie, Junjie Zhang, Bifeng Yuan, Zhijun Sun

{"title":"m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling","authors":"Shujin Li, Tian Feng, Yuantong Liu, Qichao Yang, An Song, Shuo Wang, Jun Xie, Junjie Zhang, Bifeng Yuan, Zhijun Sun","doi":"10.1038/s41368-024-00304-0","DOIUrl":"https://doi.org/10.1038/s41368-024-00304-0","url":null,"abstract":"N1-methyladenosine (m1A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 and Pten conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels. Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images 基于锥形束计算机断层扫描图像的口腔手术相关组织全自动人工智能分割

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-08 DOI: 10.1038/s41368-024-00294-z

Yu Liu, Rui Xie, Lifeng Wang, Hongpeng Liu, Chen Liu, Yimin Zhao, Shizhu Bai, Wenyong Liu

{"title":"Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images","authors":"Yu Liu, Rui Xie, Lifeng Wang, Hongpeng Liu, Chen Liu, Yimin Zhao, Shizhu Bai, Wenyong Liu","doi":"10.1038/s41368-024-00294-z","DOIUrl":"https://doi.org/10.1038/s41368-024-00294-z","url":null,"abstract":"Accurate segmentation of oral surgery-related tissues from cone beam computed tomography (CBCT) images can significantly accelerate treatment planning and improve surgical accuracy. In this paper, we propose a fully automated tissue segmentation system for dental implant surgery. Specifically, we propose an image preprocessing method based on data distribution histograms, which can adaptively process CBCT images with different parameters. Based on this, we use the bone segmentation network to obtain the segmentation results of alveolar bone, teeth, and maxillary sinus. We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks. The tooth segmentation results can obtain the order information of the dentition. The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods. Its average Dice scores on the tooth, alveolar bone, maxillary sinus, and mandibular canal segmentation tasks were 96.5%, 95.4%, 93.6%, and 94.8%, respectively. These results demonstrate that it can accelerate the development of digital dentistry.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK 苯乙双胍通过 NIBAN1 和 DDIT4 激活 ER 应激，促进口腔鳞状细胞癌细胞自噬性死亡，而与 AMPK 无关

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-08 DOI: 10.1038/s41368-024-00297-w

Dexuan Zhuang, Shuangshuang Wang, Huiting Deng, Yuxin Shi, Chang Liu, Xue Leng, Qun Zhang, Fuxiang Bai, Bin Zheng, Jing Guo, Xunwei Wu

{"title":"Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK","authors":"Dexuan Zhuang, Shuangshuang Wang, Huiting Deng, Yuxin Shi, Chang Liu, Xue Leng, Qun Zhang, Fuxiang Bai, Bin Zheng, Jing Guo, Xunwei Wu","doi":"10.1038/s41368-024-00297-w","DOIUrl":"https://doi.org/10.1038/s41368-024-00297-w","url":null,"abstract":"The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration 支架诱导缝合间充质再生的转录组和细胞解码

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-04-23 DOI: 10.1038/s41368-024-00295-y

Jiayi Wu, Feifei Li, Peng Yu, Changhao Yu, Chuyi Han, Yitian Wang, Fanyuan Yu, Ling Ye

{"title":"Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration","authors":"Jiayi Wu, Feifei Li, Peng Yu, Changhao Yu, Chuyi Han, Yitian Wang, Fanyuan Yu, Ling Ye","doi":"10.1038/s41368-024-00295-y","DOIUrl":"https://doi.org/10.1038/s41368-024-00295-y","url":null,"abstract":"Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":14.9,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0