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Evaluating the potential of an amelogenin-derived peptide in tertiary dentin formation

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Regenerative Biomaterials 2021年第2期8卷 85-93页

作者： Xiu Peng Sili Han Kun Wang Longjiang Ding Zhenqi Liu Linglin Zhang State Key Laboratory of Oral Diseases Department of Cariology and EndodonticsNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina

Several novel biomaterials have been developed for dental pulp capping by inducing tertiary dentin formation.The aim of this study was to evaluate the effect of QP5,an amelogenin-based peptide,on the mineralization of dental pulp cells(DPCs)in vitro and in vivo.The cell viability of human DPCs(hDPCs)after treatment with QP5 was determined using the Cell Counting Kit-8(CCK-8).Migration of hDPCs was assessed using scratch assays,and the pro-mineralization effect was determined using alkaline phosphatase(ALP)staining,alizarin red staining and the expression of mineralization-related genes and proteins.The results showed that QP5 had little effect on the cell viability,and significantly enhanced the migration capability of hDPCs.QP5 promoted the formation of mineralized nodules,and upregulated the activity of ALP,the expression of mRNA and proteins of mineralization-related genes.A pulp capping model in rats was generated to investigate the biological effect of QP5.The results of micro-computed tomography and haematoxylin and eosin staining indicated that the formation of tertiary dentin in QP5-capping groups was more prominent than that in the negative control group.These results indicated the potential of QP5 as a pulp therapy agent.

关键词： tertiary dentin amelogenin-derived peptide pulp capping dental pulp cells

Remineralization of enamel caries by an amelogenin-derived peptide and fluoride in vitro

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Regenerative Biomaterials 2020年第3期7卷 283-292页

作者： Longjiang Ding Sili Han Kun Wang Sainan Zheng Wenyue Zheng Xiu Peng Yumei Niu Wei Li Linglin Zhang State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of Cariology and EndodonticsWest China Hospital of StomatologySichuan UniversityChengduChina

Dental caries is one of the most common oral diseases in the world.This study was tantamount to investigate the combinatory effects of an amelogenin-derived peptide(called QP5)and fluoride on the remineralization of artificial enamel caries.The peptide QP5 was synthesized and characterized,and the binding capability of the peptide on hydroxyapatite(HA)and demineralized tooth enamel surface was analysed.Then,the mineralization function of the peptide and fluoride was studied through the spontaneous mineralization testing and remineralization on enamel caries in vitro.First,the novel peptide QP5 could bind on the hydroxyapatite and demineralized tooth enamel surfaces.Second,QP5 can transitorily stabilize the formation of amorphous calcium phosphate and direct the transformation into hydroxyapatite crystals alone and in combination with fluoride.In addition,compared to blocks treated by peptide QP5 alone or fluoride,the sample blocks showed significantly higher surface microhardness,lower mineral loss and shallower lesion depth after treatment with a combination of QP5 and fluoride at high or low concentrations.The peptide QP5 could control the crystallization of hydroxyapatite,and combinatory application of peptide QP5 and fluoride had a potential synergistic effect on the remineralization of enamel caries.

关键词： enamel caries remineralization amelogenin peptide fluoride

Transmission routes of 2019-nCoV and controlsin dental practice

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International Journal of Oral Science 2020年第1期12卷 25-30页

作者： Xian Peng Xin Xu Yuqing Li Lei Cheng Xuedong Zhou Biao Ren State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina

A novel β-coronavirus(2019-nCoV) caused severe and even fatal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-Co V,but shared the same host receptor the human angiotensin-converting enzyme 2(ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to Bat Co V Ra TG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fecal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

关键词： dental measures sharp

Microenvironmental stiffness mediates cytoskeleton re-organization in chondrocytes through laminin-FAK mechanotransduction

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International Journal of Oral Science 2022年第2期14卷 182-191页

作者： Chenchen Zhou Mengmeng Duan Daimo Guo Xinmei Du Demao Zhang Jing Xie State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina

Microenvironmental biophysical factors play a fundamental role in controlling cell behaviors including cell morphology,proliferation,adhesion and differentiation,and even determining the cell fate.Cells are able to actively sense the surrounding mechanical microenvironment and change their cellular morphology to adapt to it.Although cell morphological changes have been considered to be the first and most important step in the interaction between cells and their mechanical microenvironment,their regulatory network is not completely clear.In the current study,we generated silicon-based elastomer polydimethylsiloxane(PDMS)substrates with stiff(15:1,PDMS elastomer vs.curing agent)and soft(45:1)stiffnesses,which showed the Young’s moduli of~450 k Pa and 46 kPa,respectively,and elucidated a new path in cytoskeleton re-organization in chondrocytes in response to changed substrate stiffnesses by characterizing the axis shift from the secreted extracellular protein lamininβ1,focal adhesion complex protein FAK to microfilament bundling.We first showed the cellular cytoskeleton changes in chondrocytes by characterizing the cell spreading area and cellular synapses.We then found the changes of secreted extracellular linkage protein,lamininβ1,and focal adhesion complex protein,FAK,in chondrocytes in response to different substrate stiffnesses.These two proteins were shown to be directly interacted by Co-IP and colocalization.We next showed that impact of FAK on the cytoskeleton organization by showing the changes of microfilament bundles and found the potential intermediate regulators.Taking together,this modulation axis of lamininβ1-FAK-microfilament could enlarge our understanding about the interdependence among mechanosensing,mechanotransduction,and cytoskeleton re-organization.

关键词： laminin mec stiffness

Cell-scaffold interactions in tissue engineering for oral and craniofacial reconstruction

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Bioactive Materials 2023年第5期23卷 16-44页

作者： Fushi Wang Xinjie Cai Ya Shen Liuyan Meng The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)and Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of StomatologyWuhan UniversityWuhanChina Department of Cariology and Endodontics Hospital of StomatologyWuhan UniversityWuhanChina department of Prosthodontics Hospital of StomatologyWuhan UniversityWuhanChina Division of endodontics Department of Oral Biological and Medical SciencesFaculty of DentistryUniversity of British ColumbiaVancouverCanada

Tissue engineering(TE)is critical in oral and craniofacial reconstruction.One of the most popular topics on the biomaterial-based tissue regeneration process may be the interaction between cells and scaffolds.An increasing number of studies have identified the variables affecting cell-scaffold interaction.The creation and investigation of new scaffolds for TE and regenerative medicine based on specific interactions have become possible owing to these findings.This review discusses the effects of various types of scaffold materials on cells in TE.Because the intrinsic properties of scaffolds are essential,the influence of the physical,chemical,mechanical,and biological characteristics of scaffold materials on cell-scaffold interaction that has been discovered in recent research is elaborated in this review.The components carried by scaffolds,the degradation process,and the role of degraded products in cell-scaffold interactions are examined.Further,the roles of cells,including cell types,functions,and adhesion mechanisms,and extracellular matrix are discussed.Finally,the latest research progress on cell-scaffold interactions among various engineered tissues or organs in the oral and craniofacial region is summarized.A deeper understanding of cell-scaffold interactions is anticipated to benefit the development of TE and regenerative medicine.

关键词： Scaffolds Tissue engineering Interactions Cells

Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss

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International Journal of Oral Science 2018年第2期10卷 92-101页

作者： Kimito Hirai Hisako Furusho Kiichi Hirota Hajime Sasaki department of cariology Restorative Sciences & Endodontics University of Michigan School of Dentistry department of Immunology and Infectious Diseases The Forsyth Institute department of Oral and Maxillofacial Pathobiology Hiroshima University department of Human Stress Response Science Institute of Biomedical Science Kansai Medical University

Hypoxia（low oxygen level） is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation of hypoxia-inducible factor 1（HIF-1）.Hypoxia interferes degradation of HIF-1 alpha subunit（HIF-1α）, leading to stabilisation of HIF-1α, heterodimerization with HIF-1 beta subunit（HIF-1β） and subsequent activation of HIF-1 pathway. Apical periodontitis（periapical lesion） is a consequence of endodontic infection and ultimately results in destruction of tooth-supporting tissue, including alveolar bone. Thus far, the role of HIF-1 in periapical lesions has not been systematically examined. In the present study, we determined the role of HIF-1 in a wellcharacterised mouse periapical lesion model using two HIF-1α-activating strategies, dimethyloxalylglycine（DMOG） and adenovirusinduced constitutively active HIF-1α（CA-HIF1 A）. Both DMOG and CA-HIF1 A attenuated periapical inflammation and tissue destruction. The attenuation in vivo was associated with downregulation of nuclear factor-κappa B（NF-κB） and osteoclastic gene expressions. These two agents also suppressed NF-κB activation and subsequent production of proinflammatory cytokines by macrophages. Furthermore, activation of HIF-1α by DMOG specifically suppressed lipopolysaccharide-stimulated macrophage differentiation into M1 cells, increasing the ratio of M2 macrophages against M1 cells. Taken together, our data indicated that activation of HIF-1 plays a protective role in the development of apical periodontitis via downregulation of NF-κB, proinflammatory cytokines, M1 macrophages and osteoclastogenesis.

关键词： CA Activation hypoxia-inducible factor attenuates periapical inflammation bone loss HIF

Promoting effect of a calcium-responsive self-assemblyβ-sheet peptide on collagen intrafibrillar mineralization

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Regenerative Biomaterials 2022年第1期9卷 761-774页

作者： Zhongcheng Li Qian Ren Sili Han Longjiang Ding Xi Qin Die Hu Ting He Tian Tian Ziqian Lu Linglin Zhang State Key Laboratory of Oral Diseases National Clinical Research Centre for Oral DiseasesDepartment of Cariology and EndodonticsWest China Hospital of StomatologySichuan UniversityChengdu 610041SichuanChina department of Oral Medicine Shenzhen Stomatology HospitalShenzhen 518038GuangdongChina

Recently,a de novo synthetic calcium-responsive self-assemblyβ-sheet peptide ID8(Ile-Asp-Ile-Asp-Ile-Asp-Ile-Asp)has been developed to serve as the template inducing hydroxyapatite nucleation.The aim of this study was to evaluate the effect of ID8 on intrafibrillar mineralization of collagen making full use of its self-assembly ability.The mineralization experiments were carried out in vitro on both bare TypeⅠcollagen and fully demineralized dentin samples.The calcium-responsive self-assembly of ID8 was revealed by circular dichroism spectrum,8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate assay,attenuated total reflection Fourier transform infrared spectrum(ATR-FTIR)and transmission electron microscope(TEM).Polyacrylic acid(450 kDa)with a concentration of 100μg ml^(-1)was selected as the nucleation inhibitor based on the determination of turbidimetry and TEM with selected area electron diffraction(TEM-SAED).The results showed that collagen intrafibrillar mineralization was significantly promoted with the pretreatment of self-assembly ID8 detected by TEM-SAED,SEM,X-ray diffraction and ATRFTIR.The pretreatment of collagen utilizing self-assembly ID8 not only enhanced intermolecular hydrogen bonding but also contributed to calcium retention inside collagen and significantly increased the hydrophilicity of collagen.These results indicated that peptides with self-assembly properties like ID8 are expected to be potential tools for biomimetic mineralization of collagen.

关键词： collagen polyacrylic acid biomineralization biomimetic materials amorphous calcium phosphate

Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis

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Bone Research 2017年第3期5卷 177-194页

作者： Xin Xu Xiaoyue Jia Longyi Mo Chengcheng Liu Liwei Zheng Quan Yuan Xuedong Zhou State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University Department of Cariology and Endodontics West China Hospital of Stomatology Sichuan University department of Periodontics West China Hospital of Stomatology Sichuan University department of Pediatric Dentistry West China Hospital of Stomatology Sichuan University department of Dental Implantology West China Hospital of Stomatology Sichuan University

Postmenopausal osteoporosis （PMO） is a prevalent metabolic bone disease characterized by bone loss and structural destruction, which increases the risk of fracture in postmenopausal women. Owing to the high morbidity and serious complications of PMO, many efforts have been devoted to its prophylaxis and treatment. The intestinal microbiota is the complex community of microorganisms colonizing the gastrointestinal tract. Probiotics, which are dietary or medical supplements consisting of beneficial intestinal bacteria, work in concert with endogenous intestinal microorganisms to maintain host health. Recent studies have revealed that bone loss in PMO is closely related to host immunity, which is influenced by the intestinal microbiota. The curative effects of probiotics on metabolic bone diseases have also been demonstrated. The effects of the intestinal microbiota on bone metabolism suggest a promising target for PMO management. This review seeks to summarize the critical effects of the intestinal microbiota and probiotics on PMO, with a focus on the molecular mechanisms underlying the pathogenic relationship between bacteria and host, and to define the possible treatment options.

关键词： CHAIN FATTY-ACIDS BONE-MINERAL DENSITY TUMOR-NECROSIS-FACTOR INCREASE CALCIUM-ABSORPTION ESTROGEN-RECEPTOR-ALPHA REGULATORY T-CELLS LONG-TERM CONSUMPTION GUT MICROBIOTA VITAMIN-D PARACELLULAR PERMEABILITY

Expert consensus on digital guided therapy for endodontic diseases

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International Journal of Oral Science 2023年第4期15卷 540-551页

作者： Xi Wei Yu Du Xuedong Zhou Lin Yue Qing Yu Benxiang Hou Zhi Chen Jingping Liang Wenxia Chen Lihong Qiu Xiangya Huang Liuyan Meng Dingming Huang Xiaoyan Wang Yu Tian Zisheng Tang Qi Zhang Leiying Miao Jin Zhao Deqin Yang Jian Yang Junqi Ling department of Operative Dentistry and endodontics Hospital of StomatologyGuanghuaSchool of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Cariology 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 Operative Dentistry&endodontics School of StomatologyThe Fourth Military Medical UniversityXi’anChina department of endodontics Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina 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 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 College of Stomatology Hospital of StomatologyGuangxi Medical UniversityNanningChina department of endodontics School of StomatologyChina Medical UniversityShenyangChina department of Stomatology Xinhua HospitalShanghai Jiaotong University School of MedicineShanghaiChina department of endodontics Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoratio

Digital guided therapy(DGT)has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades.The concept of DGT for endodontic diseases is categorized into static guided endodontics(SGE),necessitating a meticulously designed template,and dynamic guided endodontics(DGE),which utilizes an optical triangulation tracking system.Based on cone-beam computed tomography(CBCT)images superimposed with or without oral scan(OS)data,a virtual template is crafted through software and subsequently translated into a 3-dimensional(3D)printing for SGE,while the system guides the drilling path with a real-time navigation in DGE.DGT was reported to resolve a series of challenging endodontic cases,including teeth with pulp obliteration,teeth with anatomical abnormalities,teeth requiring retreatment,posterior teeth needing endodontic microsurgery,and tooth autotransplantation.Case reports and basic researches all demonstrate that DGT stand as a precise,time-saving,and minimally invasive approach in contrast to conventional freehand method.This expert consensus mainly introduces the case selection,general workflow,evaluation,and impact factor of DGT,which could provide an alternative working strategy in endodontic treatment.

关键词： template utilize precise