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The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam Department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

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MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment

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Bone Research 2024年第1期12卷 153-164页

作者： Jiakang Yang Jing Shuai Lixuen Siow Jingyi Lu Miao Sun Wenyue An Mengfei Yu Baixiang Wang Qianming Chen stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310000China

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge,as chronic local inflammation can largely impair bone healing.Here,we used magnesium silicate nanospheres(MSNs)to load microRNA-146a-5p(miR-146a)to fabricate a nanobiomaterial,MSN+miR-146a,which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells(hDPSCs).In addition,miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages(BMMs)under lipopolysaccharide(LPS)stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6(TRAF6),and MSNs could simultaneously promote M2 polarization of BMMs.MiR-146a was also found to inhibit osteoclast formation.Finally,the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel.Collectively,the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oralmaxillofacial bone defects.

关键词： inflammatory healing stimulation

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Clinical relevance of distolingual roots and periodontal status in mandibular first molars: a cross-sectional study employing CBCT analysis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 244-253页

作者： Feifei MAO Meng WANG Shuai ZHOU Yan ZHAO Jiaping HUANG Fengying YIN Haiping YANG Pei-hui DING stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310016China

Objectives:Distolingual root of the permanent mandibular first molar(PMFM-DLR)has been frequently reported,which may complicate the treatment of periodontitis.This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background.Materials and methods:A total of 836 cone beam computed tomography(CBCT)images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China.Among them,complete periodontal charts were available for 69 Chinese patients with 103 teeth.Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR,bone loss,and periodontal clinical parameters,including clinical attachment loss(CAL),probing pocket depth(PPD),gingival recession(GR),and furcation involvement(FI).Results:The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4%and 26.3%,respectively.Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section,while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section.Conclusions:The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort.The morphological features of DLR were correlated with the periodontal status of mandibular first molars.This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

关键词： Distolingual root Mandibular first molar Periodontal clinical parameter Clinical attachment loss Cone beam computed tomography(CBCT)

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Glycerol solutions of highly concentrated biomineral counter-ions towards water-responsive mineralization: Demonstration on bacterial cellulose and its application in hard tissue repair

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Nano Research 2024年第3期17卷 2154-2163页

作者： Yunfei Zhao Xiaohao Liu Zhi Zhou Chaobo Feng Nan Luo Jiajun Yan Shuo Tan Yang Lu Feng Chen Bing-Qiang Lu Shisheng He Department of Orthopedic Spinal Pain Research InstituteShanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072China Department of Preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai 200011China

Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue regeneration.The current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions(a pair of cation and anion that form the corresponding minerals at certain conditions),which are stable only at very low concentrations.This typically results in inefficient mineralization and weak control over biomineral formation.Here,we find that,in the organic solvent glycerol,a variety of biomineral counter-ions(e.g.,Ca/PO_(4),Ca/CO_(3),Ca/SO_(4),Mg/PO_(4),or Fe/OH)corresponding to distinct biominerals at significantly high concentrations(up to hundreds-fold greater than those of simulated body fluid(SBF))are able to form translucent and stable solutions(mineralizing solution of highly concentrated counter-ions(MSCIs)),and mineralization can be triggered upon them with external solvents(e.g.,water or ethanol).Furthermore,with pristine bacterial cellulose(BC)membrane as a model,we demonstrate an effective and controllable mineralization performance of MSCIs on organic substrates.This approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces,but also provides regulations over mineralization rate,mineral content,phase,and dopants.The resulting mineralized BC membranes(MBCs)exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells(rBMSC).Following this,we prepare a mineralized bone suture(MBS)from MBC for non-weight bearing bone fixation,which then is tested on a rabbit median sternotomy model.It shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory response.This study,by extending the mineralization to the organic solution system of highly concentrated counter-ions,develops a promising strategy to design and build targeted mineral-based composites.

关键词： biomineralization organic solvent bacterial cellulose(BC) hard tissue repair

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Puerarin mediated miR-30b-5p targeting fibroblast activation protein against oral submucous fibrosis

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BIOCELL 2024年第4期48卷 591-599页

作者： SAIFEI XIE HUI XIE JINCAI GUO JIN TAN YULIN YU MINYI ZHANG SHANG WEN Department of Periodontal Mucosa Hunan University of Chinese MedicineChangshaChina Department of Periodontal Mucosa Changsha Stomatology HospitalChangshaChina Department of Pharmacy Changsha Stomatology HospitalChangshaChina Department of stomatology The First Hospital of Hunan University of Chinese MedicineChangshaChina

Background:Puerarin(Pue)has been reported to be a natural active ingredient with multiple antiﬁbrotic properties.This work aimed at exploring the function of Pue in oral submucousﬁbrosis(OSF)treatment.Methods:Human oral mucosaﬁbroblasts(hOMF)were induced with transforming growth factor beta1(TGF-β1)and intervened with Pue.Expressions ofﬁbrosis-related markers were analyzed by Western blot and IF staining.Cell viability was characterized by the CCK-8 assay.Expressions of miR-30 family members were quantiﬁed by qRT-PCR.The correlation betweenﬁbroblast activation protein(FAP)and miR-30 family expression was evaluated by the Pearson correlation coefﬁcient.Bioinformatics prediction and dual-luciferase reporter assay were employed to verify the regulation between FAP and miR-30b-5p.The speciﬁc mechanism of Pue on OSF was explored through the promotion or inhibition of miR-30b-5p.Results:After induction by TGF-β1,hOMF showed upregulated Collagen I,Collagen III,and FAP expressions,while miR-30 family expression was downregulated with miR-30b-5p being the most signiﬁcant.Pue intervention inhibited the excessive proliferation of TGF-β1-induced hOMF,downregulated FAP,collagen type 3(COL3A1),collagen type 1(COL1A1),matrix metalloproteinase 1(MMP1),and matrix metalloproteinase 3(MMP3)expressions,and restored miR-30 family expression.Bioinformatics prediction and dual-luciferase reporter assay revealed that miR-30b-5p selectively inhibited FAP expression.Mechanistically,miR-30b-5p mimic suppressed the excessive proliferation of TGF-β1-induced hOMF and declinedﬁbrosis levels.Pue intervention signiﬁcantly reversed the promotion of TGF-β1-induced OSF by miR-30b-5p inhibition.Conclusion:Pue mediated miR-30b-5p targeting FAP against OSF,which provided a theoretical basis for the pathogenesis research and Pue application in OSF.

关键词： Puerarin miR-30b-5p FAP Oral submucous fibrosis

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Metabolic memory:mechanisms and diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1086-1114页

作者： Hao Dong Yuezhang Sun Lulingxiao Nie Aimin Cui Pengfei Zhao Wai Keung Leung Qi Wang State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengduChina Periodontology and Implant Dentistry Division Faculty of DentistryThe University of Hong KongHong KongChina

Metabolic diseases and their complications impose health and economic burdens worldwide.Evidence from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment,such as hyperglycemia or hyperlipidemia,thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic environments.The long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and disease.Multiple molecular mechanisms collectively participate in metabolic memory management,resulting in different cellular alterations as well as tissue and organ dysfunctions,culminating in disease progression and even affecting offspring.The elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and management.Here,we retrace the history of relevant research on metabolic memory and summarize its salient characteristics.We provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular,cellular,and organ levels,with emphasis on the impact of epigenetic modulations.Finally,we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

关键词： diseases metabolism alterations

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Expert consensus on irrigation and intracanal medication in root canal therapy

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International Journal of Oral Science 2024年第1期16卷 26-35页

作者： Xiaoying Zou Xin Zheng Yuhong Liang Chengfei Zhang Bing Fan Jingping Liang Junqi Ling Zhuan Bian Qing Yu Benxiang Hou Zhi Chen Xi Wei Lihong Qiu Wenxia Chen Wenxi He Xin Xu Liuyan Meng Chen Zhang Liming Chen Shuli Deng Yayan Lei Xiaoli Xie Xiaoyan Wang Jinhua Yu Jin Zhao Song Shen Xuedong Zhou Lin Yue 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 Center of stomatology Peking University HospitalBeijingChina 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 Emergency 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 Restorative Dental Sciences EndodonticsFaculty of DentistryThe University of Hong KongPok Fu LamHong Kong SARChina 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 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 StomatologyGuanghua School of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina State Key Laboratory of Oral&Maxillofacial Reconstruction and R

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.

关键词： treatment irrigation Expert

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DLX3(Q178R)mutation delays osteogenic differentiation via H19/miR-29c-3p/KDM5B axis in TDO-iPSCs-derived MSCs

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Genes & Diseases 2024年第4期11卷 49-52页

作者： Liying Dong Na Zhao Dongmei Wang Meng Wang Yixin Zhang Liangjie Sun Chong Ding Yixiang Wang Zeyun Ma Central Laboratory Peking University School and Hospital of StomatologyBeijing 100081China Department of Oral and Maxillofacial Surgery Peking University School and Hospital of StomatologyBeijing 100081China National Engineering Laboratory for Digital and Material Technology of stomatology Peking University School and Hospital of StomatologyBeijing 100081China Beijing Key Laboratory of Digital stomatology Peking University School and Hospital of StomatologyBeijing 100081China The Second Clinical Division Peking University School and Hospital of StomatologyBeijing 100081China Department of VIP Service Peking University School and Hospital of StomatologyBeijing 100081China Department of Restorative Dentistry and Biomaterials Sciences Harvard School of Dental MedicineBostonMA 02115USA Department of Prosthodontics Fudan UniversityShanghai 200001China Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases Shanghai Stomatological HospitalFudan UniversityShanghai 200001China

Tricho-dento-osseous(TDO)syndrome is a rare autosomal dominant disease resulting from distal-less homeobox 3(DLX3)mutation.1,2 Accumulative bone density in alveolar bone is a clinically favorable phenotype for TDO patients.However,the limited number of bone marrow mesenchymal stem cells(BMSCs)in TDO patients restricts their application.

关键词： patients clinically alveolar

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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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Potential role of tubulin glutamylation in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1191-1192页

作者： Abdullah Md.Sheikh Shatera Tabassum Department of Laboratory medicine Shimane University Faculty of Medicine

The differentiation of neuronal stem cells into mature neurons is a complex process that involves both structural and functional changes. As cells undergo differentiation, there are notable functional changes, including the expression of various transcription factors, cytokines, and neurotransmitiers. Additionally, structural changes occur as the cells develop various processes from the cell body and establish synaptic contacts with other cells.

关键词： POLARITY

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