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METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs

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International Journal of Oral Science 2024年第3期16卷 528-538页

作者： Yizhou Jin Xiao Han Yuejun Wang Zhipeng Fan Beijing Key Laboratory of tooth Regeneration and Function Reconstruction Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina Research Unit of tooth Development and Regeneration Chinese Academy of Medical SciencesBeijingChina

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic ***,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic *** knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion ***,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ***,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin ***98059(a selective ERK inhibitor)blocks the corin-mediated promotion *** regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion ***,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation *** conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK *** hope this brings new insights into future clinical treatments for BRONJ.

关键词： impaired cor mediated

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PRX1-positive mesenchymal stem cells drive molar morphogenesis

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International Journal of Oral Science 2024年第2期16卷 293-305页

作者： Xiaoqiao Xu Xuyan Gong Lei Zhang Han Zhang Yao Sun Department of Implantology Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghaiChina

Mammalian teeth,developing inseparable from epithelial-mesenchymal interaction,come in many shapes and the key factors governing tooth morphology deserve to be *** merging single-cell RNA sequencing analysis with lineage tracing models,we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1^(+)cells within *** PRX1^(+)cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell *** into the mechanisms,we have discovered that Wnt5a,bestowed by mesenchymal PRX1^(+)cells,stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling *** loss of Wnt5a exhibits a defect phenotype similar to that of *** addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth *** findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

关键词： Wnt5a mesenchymal inhibited

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Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

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Genes & Diseases 2024年第1期11卷 346-357页

作者： Huanyu Luo Anahid Ahmadi Birjandi Feilong Ren Tianmeng Sun Paul T.Sharpe Hongchen Sun Zhengwen An Department of Oral Biology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China Faculty of Dentistry Oral&Craniofacial SciencesCentre for Craniofacial and Regenerative BiologyKing's College LondonLondonSE19RTUK Department of Oral Pathology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular *** contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and *** can be traced to their cells of origin and exhibit a similar ***,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent *** stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell *** mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously ***,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell *** EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample ***,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular ***,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic *** highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical *** aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

关键词： Disease Extracellular vesicles Oral tissue MSC Therapeutic application Tissue regeneration

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Copper-based nanodots as efficient biomimetic antibiotics for the treatment of oral bacterial infections Author links open overlay panel

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Particuology 2024年第8期91卷 190-201页

作者： Ying Li Nan Tang Lingling Zhao Xingfu Bao Yuzhuo Wang Zhanxin Wang Min Hu Jilin Provincial Key Laboratory of tooth Development and Bone Remodeling School and Hospital of StomatologyJilin UniversityChangchunChina Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingChina

Oral infectious diseases caused by a variety of pathogenic bacteria seriously affect the quality of ***,these diseases remain a clinical challenge because of the lack of simple,safe,and universal *** address these limitations,we synthesize CuO_(x)nanodots(CuO_(x)NDs)with excellent Fenton-like reaction activity and utilize them in the treatment of oral bacterial *** from other complicated approaches,CuO_(x)NDs are rationally prepared using a facile one-pot aqueous *** the presence of H_(2)O_(2),these well-developed CuO_(x)NDs can efficiently catalyze the generation of hydroxyl radicals(·OH)around oral pathogens,leading to the death of various ***,results of biosafety indicate the high biocompatibility and extremely low toxicity of these CuO_(x)*** understanding the admirable in vitro antibacterial effect of CuO_(x)NDs in the presence of H_(2)O_(2),we further explore their in vivo antibacterial performance on several classical animal models including oral mucosal wound model,intragingival bacteria-infected model,and the periodontal infection *** expected,these CuO_(x)NDs with wide-spectrum antibacterial activity can serve as high-performance antibacterial reagents for the treatment of various oral bacterial infections with the help of H_(2)O_(2).In brief,current nanoplatform can act as efficient antibiotics against oral pathogens with broadening the biomedical applications of copper-based nanomaterials.

关键词： Antibacterial treatment Oral diseases Fenton-likecatalytic reaction Reactive oxygen species

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Electronic structure tuning of layered double hydroxides for electrochemical sensing and its biomedical applications

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Science China Chemistry 2024年第11期 3614-3630页

作者： Kun Wang Zhiying Cao Qihang Ding Jiyoung Yoo Nem Singh Heemin Kang Lin Wang Lin Xu Jong Seung Kim School and Hospital of Stomatology Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Jilin University State Key Laboratory on Integrated Optoelectronics Collage of Electronic Science and Engineering Jilin University Department of Chemistry Korea University Department of Materials Science and Engineering Korea University

Modifying the electrodes of electrochemical sensors is critical to enhance sensitivity, selectivity, and stability, ultimately improving both their effectiveness and performance. In this paper, recent advancements in electrochemical sensors are reviewed,focusing on the utilization of layered double hydroxides(LDHs). The first section explores the advantageous and disadvantageous aspects of electrochemical sensing. Benefits include rapid response, ease of operation, and cost-effectiveness,while drawbacks concern the potential instability of prolonged use, susceptibility to interference, and the risk of biomolecule inactivation. Following this, the second section delves into the synthesis, constituents, and structure of LDHs. Moreover, after introducing the chemical mechanisms and functions of LDHs in electrochemical sensors, we concentrate on diverse modifying materials of LDHs and their different performances. Finally, the applications of LDHs in electrochemical sensing across different fields are discussed. This review aims to facilitate the continued advancement for applying LDHs in electrochemical sensors, as well as inspire the evolution of electrochemical sensing technology.

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Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

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World Journal of Stem Cells 2024年第5期16卷 560-574页

作者： Meng-Hao Lyu Ce Bian Yi-Ping Dou Kang Gao Jun-Ji Xu Pan Ma Department of Periodontics School of StomatologyCapital Medical UniversityBeijing 100050China Department of Orthodontics School of StomatologyCapital Medical UniversityBeijing 100050China Department of Dental Implantology School of StomatologyCapital Medical UniversityBeijing 100050China Beijing Key Laboratory of tooth Regeneration and Function Reconstruction School of StomatologyCapital Medical UniversityBeijing 100050China Beijing Laboratory of Oral Health Capital Medical UniversityBeijing 100050China

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be *** the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair *** To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory *** IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory *** this study,we investigated its impact on the proliferation,migration,and osteogenesis of *** expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated ***,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 *** IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of ***,STAT3 signaling plays a crucial role in the process by which IL-10 influences ***,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of *** Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of *** IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

关键词： Macrophages Interleukin-10 Bone marrow mesenchymal stem cells Signal transducer and activator of transcription 3 Inflammatory response

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Local icariin application enhanced periodontal tissue regeneration and relieved local inflammation in a minipig model of periodontitis

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International Journal of Oral Science 2018年第3期10卷 168-173页

作者： Xiuli Zhang Nannan Han Guoqing Li Haoqing Yang Yangyang Cao Zhipeng Fan Fengqiu Zhang Department of Periodontology Capital Medical University School of Stomatology Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Molecular Laboratory for Gene Therapy and tooth Regeneration Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology

Periodontitis is an inflammatory autoimmune disease. Treatment should alleviate inflammation, regulate the immune reaction and promote periodontal tissue regeneration. Icariin is the main active ingredient of Epimedii Folium, and it is a promising compound for the enhancement of mesenchymal stem cell function, promotion of bone formation, inhibition of bone resorption, alleviation of inflammation and regulation of immunity. The study investigated the effect of icariin on periodontal tissue regeneration in a minipig model of periodontitis. The minipig model of periodontitis was established. Icariin was injected locally. The periodontal clinical assessment index, a computed tomography(CT) scan, histopathology and enzyme-linked immune sorbent assay(ELISA)were used to evaluate the effects of icariin. Quantitative analysis results 12 weeks post-injection demonstrated that probing depth,gingival recession, attachment loss and alveolar bone regeneration values were(3.72 ± 1.18) mm vs.(6.56 ± 1.47) mm,(1.67 ± 0.59)mm vs.(2.38 ± 0.61) mm,(5.56 ± 1.29) mm vs.(8.61 ± 1.72) mm, and(25.65 ± 5.13) mm3 vs.(9.48 ± 1.78) mm3 in the icariin group and0.9% NaCl group, respectively. The clinical assessment, CT scan, and histopathology results demonstrated significant enhancement of periodontal tissue regeneration in the icariin group compared to the 0.9% NaCl group. The ELISA results suggested that the concentration of interleukin-1 beta(IL-1β) in the icariin group was downregulated compared to the 0.9% NaCl group, which indicates that local injection of icariin relieved local inflammation in a minipig model of periodontitis. Local injection of icariin promoted periodontal tissue regeneration and exerted anti-inflammatory and immunomodulatory function. These results support the application of icariin for the clinical treatment of periodontitis.

关键词： Local icariin application enhanced periodontal tissue regeneration and relieved local inflammation in a minipig model of periodontitis ELISA

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Primary cilia in hard tissue development and diseases

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Frontiers of Medicine 2021年第5期15卷 657-678页

作者： Sijin Li Han Zhang Yao Sun Department of Orthodontics School&Hospital of StomatologyTongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghai 200072China Department of Implantology School&Hospital of StomatologyTongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghai 200072China

Bone and teeth are hard *** tissue diseases have a serious effect on human survival and quality of *** cilia are protrusions on the surfaces of *** antennas,they are distributed on the membrane surfaces of almost all mammalian cell types and participate in the development of organs and the maintenance of *** in cilium-related genes result in a variety of developmental and even lethal *** with multiple ciliary gene mutations present overt changes in the skeletal system,suggesting that primary cilia are involved in hard tissue development and ***,primary cilia act as sensors of external stimuli and regulate bone ***,substances are trafficked through primary cilia by intraflagellar transport,which affects key signaling pathways during hard tissue *** this review,we summarize the roles of primary cilia in long bone development and remodeling from two perspectives:primary cilia signaling and sensory *** addition,the cilium-related diseases of hard tissue and the manifestations of mutant cilia in the skeleton and teeth are *** believe that all the findings will help with the intervention and treatment of related hard tissue genetic diseases.

关键词： primary cilia bone mechanical sensing hard tissue cilium-related bone disease tooth

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Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis

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Bone Research 2018年第4期6卷 408-417页

作者： Ye Li Xinxin Wang Jiali Ren Xiaoshan Wu Guoqing Li Zhipeng Fan Chunmei Zhang Ang Li Songlin Wang Molecular Laboratory for Gene Therapy and tooth Regeneration Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction School of Stomatology Capital Medical University Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University Laboratory of Molecular Signaling and Stem Cell Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction School of Stomatology Capital Medical University Department of Biochemistry and Molecular Biology Capital Medical University School of Basic Medical Sciences

Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs(miRNAs), from donors to *** are known to fine-tune a variety of biological processes, including maxillofacial development; however, the underlying mechanism remains largely unknown. In the present study, transient apoptosis was found to be due to the expression of a miniature swine maxillofacial-specific miRNA, ssc-mir-133b. Upregulation of ssc-mir-133b resulted in robust apoptosis in primary dental mesenchymal cells in the maxillofacial region. Cell leukemia myeloid 1(Mcl-1) was verified as the functional target, which triggered further downstream activation of endogenous mitochondria-related apoptotic processes during tooth *** importantly, mandible exosomes were responsible for the initial apoptosis signal. An animal study demonstrated that ectopic expression of ssc-mir-133 b resulted in failed tooth formation after 12 weeks of subcutaneous transplantation in nude mice. The tooth germ developed abnormally without the indispensable exosomal signals from the mandible.

关键词： In As

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IFT140^(+)/K14^(+) cells function as stem/progenitor cells in salivary glands

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International Journal of Oral Science 2022年第4期14卷 561-571页

作者： Xueming Zhang Ji Zhou Xinyu Wang Jiangyu Geng Yubei Chen Yao Sun Department of Oral and Maxillofacial Surgery Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationNo.399YanChang Middle RoadShanghaiChina Department of Implantology Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationNo.399YanChang Middle RoadShanghaiChina

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following ***-14^(+)(K14^(+)) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells;therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport(IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14^(+)stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140^(+)/K14^(+)could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14^(+)cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14^(+)stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140^(+)/K14^(+), for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.

关键词： salivary progenitor injuries

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