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Mitochondrial components transferred by MSC-derived exosomes promoted bone regeneration under high salt microenvironment via DRP1/Wnt signaling

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Nano Research 2024年第9期17卷 8301-8315页

作者： Yiming Wang Shuai Lin Liujing Chen Mingzhao Li Zilu Zhu Zimeng Zhuang Meilian Cai Han Zhang Chenyang Xing Weiran Li Ruili Yang Department of Orthodontics School and Hospital of StomatologyPeking UniversityBeijing 100081China National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of stomatology School and Hospital of StomatologyPeking UniversityBeijing 100081China Beijing Key Laboratory of Digital stomatology School and Hospital of StomatologyPeking UniversityBeijing 100081China

Bone homeostasis relies on the dynamic balance of osteoblast mediated bone construction and osteoclast-based bone resorption processes,which has been reported to be controlled by various mineral ***,there is no direct evidence of the effect and the underlying mechanism of high salt stimulation on bone *** this study,we demonstrated that high salt stimulation promoted excessive mitochondrial fission mediated by dynamin-related protein 1 in mesenchymal stem cells,which resulted in impaired mitochondrial morphology and ***,this impairment hindered the bone formation of mesenchymal stem cells,resulting in osteopenia in ***,the impaired property of mesenchymal stem cells which was caused by high salt was controlled by dynamin-related protein 1 mediated mitochondrial fission,which inhibited the classical Wnt signaling ***,the osteogenic property of mesenchymal stem cells decreased by high salt could be restored by exosomes to transfer the mitochondrial DNA into the impaired mesenchymal stem *** study provides not only new strategies for promoting bone regeneration but also new insights into the effect and mechanism of exosome-mediated delivery.

关键词： high salt dynamin-related protein 1 mitochondrial injury exosomes bone regeneration

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3D-printed Mg-1Ca/polycaprolactone composite scaffolds with promoted bone regeneration

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Journal of Magnesium and Alloys 2024年第3期12卷 966-979页

作者： Xiao Zhao Siyi Wang Feilong Wang Yuan Zhu Ranli Gu Fan Yang Yongxiang Xu Dandan Xia Yunsong Liu Department of Prosthodontics Peking University School and Hospital of StomatologyBeijing 100081China National Center of stomatology National Engineering Laboratory for Digital and Material Technology of StomatologyNational Clinical Research Center for Oral DiseasesBeijing Key Laboratory of Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing 100081China Department of Dental Materials Peking University School and Hospital of StomatologyBeijing 100081China

In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its *** this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these *** used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling *** explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL *** 5 and 10 wt%Mg-1Ca/PCL composites were found to have good ***,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure *** vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and *** tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone *** results indicated that the Wnt/β-catenin pathway was involved in the osteogenic ***,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical *** of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone ***,there remain many limitations in the materials and manufacturing methods used to fabricate *** study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation ***,the fused deposition modeling method allows precise control of the macroscopic morphology and microsc

关键词： 3D printing Bone tissue engineering Magnesium Osteogenic Polycaprolactone Scaffold.

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Regulating Blood Clot Fibrin Films to Manipulate Biomaterial-Mediated Foreign Body Responses

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Research 2024年第2期2023卷 565-581页

作者： Yang Zou Zhengjie Shan Zongpu Han Jieting Yang Yixiong Lin Zhuohong Gong Lv Xie Jieyun Xu Runlong Xie Zhuofan Chen Zetao Chen Hospital of stomatology Guanghua School of StomatologySun Yat-sen University and Guangdong Research Center for Dental and Cranial Rehabilitation and Material EngineeringGuangzhou 510055China

The clinical efficacy of implanted biomaterials is often compromised by host immune recognition and subsequent foreign body responses(FBRs).During the implantation,biomaterials inevitably come into direct contact with the blood,absorbing blood protein and forming blood *** studies have been carried out to regulate protein adsorption,thus manipulating ***,the role of clot surface fibrin films formed by clotting shrinkage in host reactions and FBR is often *** of the principle of fibrin film formation being relevant to fibrinogen or clotting factor absorption,it is feasible to manipulate the fibrin film formation via tuning the absorption of fibrinogen and clotting *** biological hydroxyapatite reserved bone architecture and microporous structure,the smaller particle size may expose more microporous structures and adsorb more fibrinogen or clotting ***,we set up 3 sizes(small,<0.2 mm;medium,1 to 2 mm;large,3 to 4 mm)of biological hydroxyapatite(porcine bone-derived hydroxyapatite)with different microporous structures to investigate the absorption of blood protein,the formation of clot surface fibrin films,and the subsequent *** found that small group adsorbed more clotting factors because of more microporous structures and formed the thinnest and sparsest fibrin *** thinnest and sparsest fibrin films increased inflammation and profibrosis of macrophages through a potential signaling pathway of cell adhesion-cytoskeleton-autophagy,leading to the stronger *** group adsorbed lesser clotting factors,forming the thickest and densest fibrin films,easing inflammation and profibrosis of macrophages,and finally mitigating ***,this study deepens the understanding of the role of fibrin films in host recognition and FBR and demonstrates the feasibility of a strategy to regulate FBR by modulating fibrin films via tuning the absorption of blood proteins.

关键词： Blood subsequent biomaterials

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More than just aligning the teeth:Clear aligners with multifunctional prowess

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Nano Research 2024年第8期17卷 7665-7674页

作者： Yang Chen Lei-Ming Cao Nian-Nian Zhong Zi-Zhan Li Lin-Lin Bu Fang-Yi Huo Hong He State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool and Hospital of StomatologyWuhan UniversityWuhan 430079China Department of Oral and Maxillofacial-Head Neck Oncology School and Hospital of StomatologyWuhan UniversityWuhan 430079China Department of Zhuankou Clinical Branches School and Hospital of StomatologyWuhan UniversityWuhan 430000China Department of Orthodontics School and Hospital of StomatologyWuhan UniversityWuhan 430079China

With the increasing demand for beauty and health,clear aligners(CAs)have been widely applied among patients with ***,patients treated with CAs also face some potential complications,such as demineralization,dental caries,and periodontal *** addition,some patients have additional needs to improve their quality of life,such as bleaching *** order to prevent or solve these problems,the modification of CAs is a promising method because their extensive long-term contact with tooth surfaces makes them ideal devices for implementing adjuvant medical *** this review,we discuss various advanced CAs with medical functions based on the clinical needs of *** far as we know,the additional functions of CAs mainly include antibacterial,remineralization,whitening,and accelerating tooth *** functions are achieved by two major pathways,the combination of CAs with drugs/biomaterials and increasing the capacity or affinity of *** addition,we discuss the current limitations of in vitro experiments which are designed to explore the effectiveness and properties of novel CAs,and the challenges of bringing a multifunctional appliance from proposal to clinical *** the end of this review,we provide insights into the broader prospects for the improvement of CAs.

关键词： advanced clear aligners medical device modification drug delivery system personalized medicine

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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

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International Journal of Oral Science 2024年第3期16卷 515-527页

作者： Guowu Gan Shihan Lin Yufang Luo Yu Zeng Beibei Lu Ren Zhang Shuai Chen Huaxiang Lei Zhiyu Cai Xiaojing Huang Fujian Key Laboratory of Oral Diseases&Fujian Provincial Engineering Research Center of Oral Biomaterial&stomatology Key Laboratory of Fujian College and University School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Institute of stomatology&Research Center of Dental and Craniofacial Implants School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of stomatology Fujian Medical University Union HospitalFuzhouChina

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 *** 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 ***,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was *** increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular *** conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD *** 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.

关键词： atherosclerosis metabolism impaired

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Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

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World Journal of Stem Cells 2024年第3期16卷 267-286页

作者： Tong Wu Fu Zheng Hong-Yi Tang Hua-Zhi Li Xin-Yu Cui Shuai Ding Duo Liu Cui-Ying Li Jiu-Hui Jiang Rui-Li Yang Department of Orthodontics Peking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China Department of Central Laboratory Peking University School and Hospital of StomatologyNational Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China

BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root ***-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture *** is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still *** To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying *** A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue *** vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red *** expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via *** The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),*** could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by ***,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by ***,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA ***,LIPUS increased alveolar

关键词： Low-intensity pulsed ultrasound Bone resorption Osteogenesis Cytoskeleton-Lamin A/C-Yes-associated protein axis Bone marrow mesenchymal stem cells Orthodontic tooth movement

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Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

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International Journal of Oral Science 2024年第1期16卷 163-172页

作者： Xiao Yang Hui Zhao Rui Li Yang Chen Zhi Xu Zhengjun Shang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina Department of Oral and Maxillofacial-Head and Neck Oncology School of Stomatology–Hospital of StomatologyWuhan UniversityWuhanChina Department of stomatology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

关键词： angiogenesis elevated endogenous

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Genomic alterations in oral multiple primary cancers

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International Journal of Oral Science 2024年第1期16卷 145-153页

作者： Wen Wang Qian Wang Shiying Sun Pengfei Zhang Yuyu Li Weimin Lin Qiwen Li Xiao Zhang Zhe Ma Haiyan Lu Hebei Key Laboratory of stomatology Hebei Clinical Research Center for Oral DiseasesHebei Medical UniversityShijiazhuangChina Department of Orthodontics School and Hospital of StomatologyHebei Medical UniversityShijiazhuangChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&West China Hospital of stomatology Sichuan UniversityChengduChina Department of Preventive Dentistry School and Hospital of StomatologyHebei Medical UniversityShijiazhuangHebeiChina

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in ***, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

关键词： alterations metastasis oral

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Expert consensus on difficulty assessment of endodontic therapy

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International Journal of Oral Science 2024年第1期16卷 15-25页

作者： Dingming Huang Xiaoyan Wang Jingping Liang Junqi Ling Zhuan Bian Qing Yu Benxiang Hou Xinmei Chen Jiyao Li Ling Ye Lei Cheng Xin Xu Tao Hu Hongkun Wu Bin Guo Qin Su Zhi Chen Lihong Qiu Wenxia Chen Xi Wei Zhengwei Huang Jinhua Yu Zhengmei Lin Qi Zhang Deqin Yang Jin Zhao Shuang Pan Jian Yang Jiayuan Wu Yihuai Pan Xiaoli Xie Shuli Deng Xiaojing Huang Lan Zhang Lin Yue Xuedong Zhou State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&Department of Operative Dentistry and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesNational Center for StomatologyShanghai Key Laboratory of StomatologyShanghaiChina Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghuaSchool of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina The State Key Laboratory Breeding Base of Basic Science of stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of StomatologyWuhan UniversityWuhanChina Department of Operative Dentistry&Endodontics School of StomatologyThe Fourth Military Medical UniversityXi’anChina Department of Endodontics Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&Department of Preventive Dentistry West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&Department of Geriatric dentistry West China Hospital of Stomatology

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

关键词： anatomy difficulty treatment

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A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

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Nano Research 2024年第6期17卷 5424-5434页

作者： Jinna Ren Jingying Hu Fan Dong Yan Xu Yang Peng Yuping Qian Guanmeng Zhang Min Wang Yuguang Wang Department of Prosthodontics Hospital of StomatologyJilin UniversityChangchun 130021China Department of General Dentistry II Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Center of Digital Dentistry Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Nursing Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China The VIP Department School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseasesShenyang 110002China

Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic ***,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune *** this basis,the editor can be combined with optical therapy to improve patient *** this study,the metal ratio was regulated in response to the nanocarrier of acid response ***,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell *** on these results,the nanoparticles were cracked in an acidic environment and then released copper ***,the nanoparticles contributed to cuprotosis and immunogenic *** addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without *** rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for ***,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell *** all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

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