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Journal of Materials Science & Technology 2019年第9期35卷 1894-1905页

作者： Mingli Lin Huanhuan Liu Jingjing Deng Ran An Minjuan Shen Yanqiu Li Xu Zhang School of Stomatology Hospital of Stomatology Tianjin Medical University

The significant role of the polyelectrolytic nature of non-collagenous proteins (NCPs) in regulating the in vivo mineralization of collagen provides important insights for scientists searching for analogues of NCPs to achieve in vitro collagen mineralization. Polyampholyte carboxymethyl chitosan (CMC) has both carboxyl and amino groups, which allows it to act as a cationic or anionic polyelectrolyte below or above its isoelectric point (IP), respectively. In this study, CMC was employed as the analogue of NCPs to stabilize amorphous calcium phosphate (ACP) under acidic conditions (pH < 3.5) via the formation of CMC/ACP nanocomplexes. In the presence of both ACP nanoparticles and acid collagen molecules, ACP nanoparticles could be integrated into collagen fibrils during the process of collagen self-assembly and achieve intrafibrillar mineralization of collagen in vitro (i.e., synchronous self-assembly/mineralization (SSM) of collagen). This mode of mineralization is different from established mechanisms in which mineralization follows the self-assembly (MFS) of collagen. Thus, SSM provides a new strategy for developing materials from mineralized collagen scaffolds.

关键词： Synchronous self-assembly/mineralization Intrafibrillar mineralization Polyampholyte Carboxymethyl chitosan Amorphous calcium phosphate

Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis

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Bioactive Materials 2023年第4期22卷 326-342页

作者： Jun Tian Weiyang Chen Yuhua Xiong Qianer Li Siyi Kong Mengjie Li Chunfeng Pang Yu Qiu Zhezhen Xu Qimei Gong Xi Wei Hospital of stomatology Guanghua School of StomatologySun Yat-Sen UniversityGuangzhouGuangdong510055PR China Guangdong Provincial Key Laboratory of stomatology GuangzhouGuangdong510055PR China

Extensive macrophage inflammatory responses and osteoclast formation are predominant during inflammatory or infective osteolysis.Mesenchymal stem cell(MSC)-derived small extracellular vesicles(MSC-sEV)have been shown to exert therapeutic effects on bone defects.However,cultured MSCs are typically exposed to normoxia(21%O2)in vitro,which differs largely from the oxygen concentration in vivo under hypoxic conditions.It is largely unknown whether sEV derived from dental pulp stem cells(DPSCs)cultured under hypoxic conditions(Hypo-sEV)exert better therapeutic effects on lipopolysaccharide(LPS)-induced inflammatory osteolysis than those cultured under normoxic conditions(Nor-sEV)by simultaneously inhibiting the macrophage inflammatory response and osteoclastogenesis.In this study,we show that hypoxia significantly induces the release of sEV from DPSCs.Moreover,Hypo-sEV exhibit significantly improved efficacy in promoting M2 macrophage polarization and suppressing osteoclast formation to alleviate LPS-induced inflammatory calvarial bone loss compared with Nor-sEV.Mechanistically,hypoxia preconditioning markedly alters the miRNA profiles of DPSC-sEV.MiR-210-3p is enriched in Hypo-sEV,and can simultaneously induce M2 macrophage generation and inhibit osteoclastogenesis by targeting NF-κB1 p105,which attenuates osteolysis.Our study suggests a promising potential for hypoxia-induced DPSC-sEV to treat inflammatory or infective osteolysis and identifies a novel role of miR-210-3p in concurrently hindering osteoclastogenesis and macrophage inflammatory response by inhibiting NF-kB1 expression.

关键词： Dental pulp stem cells Small extracellular vesicles Macrophage Osteoclast Inflammatory osteolysis

Improving hard metal implant and soft tissue integration by modulating the“inflammatory-fibrous complex”response

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Bioactive Materials 2023年第2期20卷 42-52页

作者： Peina Huang Jieyun Xu Lv Xie Guangqi Gao Shoucheng Chen Zhuohong Gong Xiaomei Lao Zhengjie Shan Jiamin Shi Zhaocai Zhou Zhuofan Chen Yang Cao Yan Wang Zetao Chen Hospital of stomatology Guanghua School of StomatologySun Yat-sen University and Guangdong Provincial Key Laboratory of StomatologyNo.56Lingyuan West RoadYuexiu DistrictGuangzhou510055China

Soft tissue integration is one major difficulty in the wide applications of metal materials in soft tissue-related areas.The inevitable inflammatory response and subsequent fibrous reaction toward the metal implant is one key response for metal implant-soft tissue integration.It is of great importance to modulate this inflammatory-fibrous response,which is mainly mediated by the multidirectional interaction between fibroblasts and macrophages.In this study,macrophages are induced to generate M1 and M2 macrophage immune microenvironments.Their cytokine profiles have been proven to have potentially multi-regulatory effects on fibroblasts.The multi-reparative effects of soft tissue cells(human gingival fibroblasts)cultured on metal material(titanium alloy disks)in M1 and M2 immune microenvironments are then dissected.Fibroblasts in the M1 immune microenvironment tend to aggravate the inflammatory response in a pro-inflammatory positive feedback loop,while M2 immune microenvironment enhances multiple functions of fibroblasts in soft tissue integration,including soft tissue regeneration,cell adhesion on materials,and contraction to immobilize soft tissue.Enlighted by the close interaction between macrophages and fibroblasts,we propose the concept of an“inflammatory-fibrous complex”to disclose possible methods of precisely and effectively modulating inflammatory and fibrous responses,thus advancing the development of metal soft tissue materials.

关键词： Inflammation Soft tissue Macrophage Fibroblast Metal material

Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2021年第5期22卷 410-420页

作者： Baixiang WANG Jiakang YANG Lijie FAN YuWANG Chenqiu ZHANG HuimingWANG The Affiliated Hospital of stomatology School of StomatologyZhejiang University School of Medicineand Key Laboratory of Oral Biomedical Research of Zhejiang ProvinceHangzhou 310006China School of Stomatology Zhejiang University School of MedicineHangzhou 310006China

Hypertension is a prevalent systemic disease in the elderly,who can suffer from several pathological skeletal conditions simultaneously,including osteoporosis.Benidipine(BD),which is widely used to treat hypertension,has been proved to have a beneficial effect on bone metabolism.In order to confirm the osteogenic effects of BD,we investigated its osteogenic function using mouse MC3T3-E1 preosteoblast cells in vitro.The proliferative ability of MC3T3-E1 cells was significantly associated with the concentration of BD,as measured by methylthiazolyldiphenyl-tetrazolium bromide(MTT)assay and cell cycle assay.With BD treatment,the osteogenic differentiation and maturation of MC3T3-E1 cells were increased,as established by the alkaline phosphatase(ALP)activity test,matrix mineralized nodules formation,osteogenic genetic test,and protein expression analyses.Moreover,our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD,while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK(receptor activator of nuclear factor-κB(NF-κB))pathway.The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study.

关键词： Benidipine Osteoblast Osteogenesis MC3T3-E1

Transcriptional activation of glucose transporter 1 in orthodontic tooth movement-associated mechanical response

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International Journal of Oral Science 2018年第4期10卷 244-252页

作者： Yu Wang Qian Li Fuliang Liu Shanshan Jin Yimei Zhang Ting Zhang Yunyan Zhu Yanheng Zhou Department of Orthodontics Peking University School and Hospital of StomatologyBeijingChina National Engineering Laboratory for Digital and Material Technology of stomatology Peking University School and Hospital of StomatologyBeijingChina Beijing Key Laboratory of Digital stomatology Peking University School and Hospital of StomatologyBeijingChina

The interplay between mechanoresponses and a broad range of fundamental biological processes, such as cell cycle progression,growth and differentiation, has been extensively investigated. However, metabolic regulation in mechanobiology remains largely unexplored. Here, we identified glucose transporter 1(GLUT1)—the primary glucose transporter in various cells—as a novel mechanosensitive gene in orthodontic tooth movement(OTM). Using an in vivo rat OTM model, we demonstrated the specific induction of Glut1 proteins on the compressive side of a physically strained periodontal ligament. This transcriptional activation could be recapitulated in in vitro cultured human periodontal ligament cells(PDLCs), showing a time-and dose-dependent mechanoresponse. Importantly, application of GLUT1 specific inhibitor WZB117 greatly suppressed the efficiency of orthodontic tooth movement in a mouse OTM model, and this reduction was associated with a decline in osteoclastic activities. A mechanistic study suggested that GLUT1 inhibition affected the receptor activator for nuclear factor-κ B Ligand(RANKL)/osteoprotegerin(OPG)system by impairing compressive force-mediated RANKL upregulation. Consistently, pretreatment of PDLCs with WZB117 severely impeded the osteoclastic differentiation of co-cultured RAW264.7 cells. Further biochemical analysis indicated mutual regulation between GLUT1 and the MEK/ERK cascade to relay potential communication between glucose uptake and mechanical stress response. Together, these cross-species experiments revealed the transcriptional activation of GLUT1 as a novel and conserved linkage between metabolism and bone remodelling.

关键词： Transcriptional activation of glucose transporter 1 in orthodontic tooth movement-associated mechanical response OTM RANKL

Long-term follow-up of a patient with venlafaxine-induced diurnal bruxism treated with an occlusal splint:A case report

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World Journal of Clinical Cases 2019年第4期7卷 516-524页

作者： Jia-Min Chen Ying Yan Department of Prosthodontics Guanghua School of StomatologyHospital of Stomatology Sun Yat-sen University Guangdong Provincial Key Laboratory of Stomatology

BACKGROUND Bruxism is a jaw-muscle activity characterized by the clenching or grinding of teeth. It can be divided into nocturnal bruxism and diurnal bruxism(DB). DB secondary to antidepressants is rare and refractory. Reports associated with antidepressant-induced DB are mostly anecdotal without long-term follow-up.The effect of drug intervention on antidepressant-induced DB is still contested.We herein report the first case of successful treatment of venlafaxine-induced DB with an occlusal splint.CASE SUMMARY This case report describes detailed 7-year follow-up of a patient with venlafaxineinduced DB treated with an occlusal splint. The patient who complained about involuntary daytime tooth grinding after taking venlafaxine for a period of 4 mo and was diagnosed with venlafaxine-induced DB. Subsequently, an occlusal splint with modified bilateral buccal-pterygoid pads was used to treat his tooth grinding and to protect the dental structures from tooth wearing. The patient reported remission of symptoms after several months of treatment. His grinding activity was gradually and stably controlled after 2 years, with an almost complete recovery from DB after 6 years.CONCLUSION The maxillary buccal-pterygoid splint can be used as a noninvasive approach to treat venlafaxine-induced DB.

关键词： Occlusal splint Venlafaxine Diurnal bruxism Tooth grinding Movement disorders Treatment Case report

Extrapolating neurogenesis of mesenchymal stem/stromal cells on electroactive and electroconductive scaffolds to dental and oral-derived stem cells

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International Journal of Oral Science 2022年第2期14卷 123-131页

作者： Boon Chin Heng Yunyang Bai Xiaochan Li Xuehui Zhang Xuliang Deng Central Laboratory Peking University School and Hospital of StomatologyBeijingChina school of Medical and Life Sciences Sunway UniversitySubang JayaSelangor Darul EhsanMalaysia Department of Geriatric Dentistry Peking University School and Hospital of StomatologyBeijingChina Department of Dental Materials&Dental Medical Devices Testing Center Peking University School and Hospital of StomatologyBeijingChina National Engineering Laboratory for Digital and Material Technology of stomatology NMPA Key Laboratory for Dental MaterialsBeijing Laboratory of Biomedical Materials&Beijing Key Laboratory of Digital StomatologyPeking University School and Hospital of StomatologyBeijingChina

The high neurogenic potential of dental and oral-derived stem cells due to their embryonic neural crest origin,coupled with their ready accessibility and easy isolation from clinical waste,make these ideal cell sources for neuroregeneration therapy.Nevertheless,these cells also have high propensity to differentiate into the osteo-odontogenic lineage.One strategy to enhance neurogenesis of these cells may be to recapitulate the natural physiological electrical microenvironment of neural tissues via electroactive or electroconductive tissue engineering scaffolds.Nevertheless,to date,there had been hardly any such studies on these cells.Most relevant scientific information comes from neurogenesis of other mesenchymal stem/stromal cell lineages(particularly bone marrow and adipose tissue)cultured on electroactive and electroconductive scaffolds,which will therefore be the focus of this review.Although there are larger number of similar studies on neural cell lines(i.e.PC12),neural stem/progenitor cells,and pluripotent stem cells,the scientific data from such studies are much less relevant and less translatable to dental and oral-derived stem cells,which are of the mesenchymal lineage.Much extrapolation work is needed to validate that electroactive and electroconductive scaffolds can indeed promote neurogenesis of dental and oral-derived stem cells,which would thus facilitate clinical applications in neuroregeneration therapy.

关键词： mesenchymal conductive neural

Expert consensus on regenerative endodontic procedures

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International Journal of Oral Science 2022年第4期14卷 411-423页

作者： Xi Wei Maobin Yang Lin Yue Dingming Huang Xuedong Zhou Xiaoyan Wang Qi Zhang Lihong Qiu Zhengwei Huang Hanguo Wang Liuyan Meng Hong Li Wenxia Chen Xiaoying Zou Junqi Ling Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghua School of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouGuangdongChina Department of Endodontology Maurice H Kornberg School of DentistryTemple UniversityPhiladelphiaPennsylvaniaUSA 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 State Key Laboratory of Oral Diseases&Department of Operative Dentistry and Endodontics West China Hospital of StomatologyNational Centerof StomatologyNational Clinical Research Centre for Oral Diseases Sichuan UniversityChengduChina Department of Endodontics Stomatological Hospital and Dental School ofTongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghaiChina Department of Endodontics School of StomatologyChina Medical UniversityShenyangLiaoningChina 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&Endodontics School of StomatologyThe Fourth Military Medical UniversityXi'anChina 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 Bejing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina College of Stomatol

Regenerative endodontic procedures(REPs)is a biologic-based treatment modality for immature permanent teeth diagnosed with pulp necrosis.The ultimate objective of REPs is to regenerate the pulp-dentin complex,extend the tooth longevity and restore the normal function.Scientific evidence has demonstrated the efficacy of REPs in promotion of root development through case reports,case series,cohort studies,and randomized controlled studies.However,variations in clinical protocols for REPs exist due to the empirical nature of the original protocols and rapid advancements in the research field of regenerative endodontics.The heterogeneity in protocols may cause confusion among dental practitioners,thus guidelines and considerations of REPs should be explicated.This expert consensus mainly discusses the biological foundation,the available clinical protocols and current status of REPs in treating immature teeth with pulp necrosis,as well as the main complications of this treatment,aiming at refining the clinical management of REPs in accordance with the progress of basic researches and clinical studies,suggesting REPs may become a more consistently evidence-based option in dental treatment.

关键词： treatment Expert promotion

Effects of Ginsenoside Rg-1 on the Proliferation and Osteogenic Differentiation of Human Periodontal Ligament Stem Cells

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Chinese Journal of Integrative Medicine 2015年第9期21卷 676-681页

作者：殷丽华程文晓秦子顺孙可墨钟梅王家奎高维岳余占海 School of Stomatology Lanzhou University

Objective： TO evaluate the effects of ginsenoside Rg-1 on the proliferation and osteogenic differentiation of human periodontal ligament stem cells （hPDLSCs） and to explore the possible application on the alveolar bone regeneration. Methods： To determine the optimum concentration, the effects of ginsenoside Rg-1 ranging from 10 to 100 μmol/L were evaluated by 3-（4,5）-dimethylthiahiazo（-z-yl）-3,5-di-phenytetrazoliumromide, alkaline phosphatase activity and calcium deposition. Expressions of runt-related transcription factor 2, collagen alpha-2（I） chain, osteopontin, osteocalcin protein were examined using real-time polymerase chain reaction. Results： Compared with the control group, a certain concentration （10 μmol/L） of the Rg-1 solution significantly enhanced the proliferation and osteogenic differentiation of hPDLSCs （P〈0.05）. However, concentrations that exceeds 100 μmol/L led to cytotoxicity whereas concentrations below 10 nmol/L showed no significant effect as compared with the control. Conclusion： Ginsenoside Rg-1 can enhance the proliferation and osteogenic differentiation of hPDLSCs at an optimal concentration of 10 μmol/L.

关键词： ginsenoside Rg-1 osteogenic differentiation proliferation human periodontal ligament stem cell Chinese medicine

Correlations among core species corresponding to the clinical staging of periodontitis

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BIOCELL 2023年第2期47卷 431-439页

作者： QIAN ZHANG MIN ZHEN PENG LI XIAOPEI CHI YIFEI ZHANG Central Laboratory Peking University School and Hospital of StomatologyBeijing Key Laboratory of Digital StomatologyNational Center of StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Department of Periodontology Peking University School and Hospital of StomatologyBeijingChina Second Clinical Division Peking University School and Hospital of StomatologyBeijingChina Department of Geriatric Dentistry Peking University School and Hospital of StomatologyBeijingChina

The correlation between microbiota plays a vital role in the progression of periodontal disease.This study investigated the in situ interaction networks between periodontal pathogens in periodontal and peri-implant disease.We used quantitative real-time polymerase chain reaction and Pearson’s correlation coefficients to quantify the copy numbers and correlations of four oral core species—Fusobacterium nucleatum,Porphyromonas gingivalis,Prevotella intermedia,and Streptococcus gordonii—from 80 subgingival sites(healthy and with periodontitis or gingivitis)in patients with periodontitis,and 68 subgingival sites(healthy and with periodontitis,gingivitis,peri-implantitis,or peri-implant mucositis)in patients with implants.The highest bacterial counts were observed for Porphyromonas gingivalis and Prevotella intermedia at all the sites.Within the same cohorts,the bacterial loads were greater at diseased sites than at healthy sites.Bacterial counts did not differ among clinical sites in the same group(P>0.05)but differed between periodontitis and peri-implant mucositis sites in the two groups.Porphyromonas gingivalis,F.nucleatum,and Prevotella intermedia had strong correlations at gingivitis and healthy sites and moderate correlations at periodontitis sites in patients with periodontitis.In patients with implants,Prevotella intermedia,F.nucleatum,and S.gordonii had strong correlations only at peri-implantitis sites.Also,based on metagenomic analysis,F.nucleatum and Prevotella intermedia were significantly correlated at the subgingival plaque in peri-implantitis and periodontitis samples.Our results suggest that variations in microbe-microbe interactions in subgingival plaque reflect changes in the progression of periodontal disease,providing a new perspective for understanding the mechanisms of periodontitis and peri-implantitis.

关键词： Quantitative polymerase chain reaction Bacterial correlation Bacterial counts