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8101MCID_676f085dcd62a98c9f0bab67 38927412 Dazhuang Lu[author] Lu, Dazhuang[Full Author Name] lu, dazhuang[Author] trying2...
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2227-90591262024May29BiomedicinesBiomedicinesM2 Macrophages Guide Periosteal Stromal Cell Recruitment and Initiate Bone Injury Regeneration.120510.3390/biomedicines12061205The periosteum plays a critical role in bone repair and is significantly influenced by the surrounding immune microenvironment. In this study, we employed 10× single-cell RNA sequencing to create a detailed cellular atlas of the swine cranial periosteum, highlighting the cellular dynamics and interactions essential for cranial bone injury repair. We noted that such injuries lead to an increase in M2 macrophages, which are key in modulating the periosteum's immune response and driving the bone regeneration process. These macrophages actively recruit periosteal stromal cells (PSCs) by secreting Neuregulin 1 (NRG1), a crucial factor in initiating bone regeneration. This recruitment process emphasizes the critical role of PSCs in effective bone repair, positioning them as primary targets for therapeutic interventions. Our results indicate that enhancing the interaction between M2 macrophages and PSCs could significantly improve the outcomes of treatments aimed at cranial bone repair and regeneration.LuDazhuangD0000-0001-5681-5282Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.ZhangYingfeiYDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.LiangShiminSDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.LiYangYDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.QingJiaJDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.GuLanxinL0000-0003-1094-2205Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.XuXiuyunXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.WangZeyingZ0000-0003-1606-9937Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.GaoXinXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.LiuHaoHDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.ZhangXiaoXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.ZhouYongshengY0000-0002-4332-0878Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.ZhangPingP0000-0001-8651-2100Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Institute of Advanced Clinical Medicine, Peking University, No.38 Xueyuan Road, Haidian District, Beijing 100191, China.eng81930026National Natural Science Foundation of ChinaJournal Article20240529
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1873-27631872024OctBoneBoneUBE2C orchestrates bone formation through stabilization of SMAD1/5.11717511717510.1016/j.bone.2024.117175S8756-3282(24)00164-9While previous studies have demonstrated the role of ubiquitin-conjugating enzyme 2C (UBE2C) in promoting β-cell proliferation and cancer cell lineage expansion, its specific function and mechanism in bone marrow mesenchymal stem/stromal cells (BMSCs) growth and differentiation remain poorly understood. Our findings indicate that mice with conditional Ube2c deletions in BMSCs and osteoblasts exhibit reduced skeletal bone mass and impaired bone repair. A significant reduction in the proliferative capacity of BMSCs was observed in conditional Ube2c knockout mice, with no effect on apoptosis. Additionally, conditional Ube2c knockout mice exhibited enhanced osteoclastic activity and reduced osteogenic differentiation. Furthermore, human BMSCs with stable UBE2C knockdown exhibited diminished capacity for osteogenic differentiation. Mechanistically, we discovered that UBE2C binds to and stabilizes SMAD1/5 protein expression levels. Interestingly, UBE2C's role in regulating osteogenic differentiation and SMAD1/5 expression levels appears to be independent of its enzymatic activity. Notably, UBE2C regulates osteogenic differentiation through SMAD1/5 signaling. In conclusion, our findings underscore the pivotal role of UBE2C in bone formation, emphasizing its contribution to enhanced osteogenic differentiation through the stabilization of SMAD1/5. These results propose UBE2C as a promising target for BMSC-based bone regeneration.Copyright © 2024. Published by Elsevier Inc.ZhangHuiHDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.DuYanggeYDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.LuDazhuangDDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.WangXuXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.LiYangYDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.QingJiaJDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.ZhangYingfeiYDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.LiuHaoHDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.LvLongweiLDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.ZhangXiaoXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.LiuYunsongYDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China.ZhouYongshengYDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China. Electronic address: kqzhouysh@hsc.pku.edu.cn.ZhangPingPDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & National Health Commission Key Laboratory of Digital Technology of Stomatology, 22 Zhongguancun South Avenue, Haidian District, 100081 Beijing, China. Electronic address: zhangping332@bjmu.edu.cn.engJournal Article20240623
United StatesBone85040481873-27630Smad1 ProteinEC 2.3.2.23Ubiquitin-Conjugating Enzymes0Smad5 ProteinIMAnimalsOsteogenesisphysiologySmad1 ProteinmetabolismUbiquitin-Conjugating EnzymesmetabolismHumansCell DifferentiationphysiologyMice, KnockoutSmad5 ProteinmetabolismMesenchymal Stem CellsmetabolismcytologyMiceSignal TransductionCell ProliferationProtein StabilityOsteoblastsmetabolismOsteoclastsmetabolismcytologyBMSCsBone formationSMAD1SMAD5UBE2CDeclaration of competing interest The authors declare no competing interests.202454202461820246192024815042202462604220246251918ppublish3891796310.1016/j.bone.2024.117175S8756-3282(24)00164-9380136182024070820240710
2576-2095732024JunAnimal models and experimental medicineAnimal Model Exp MedCinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways.208221208-22110.1002/ame2.12359Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength. However, current anti-resorptive drugs carry a risk of various complications. The deep learning-based efficacy prediction system (DLEPS) is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes. This study aimed to explore the protective effect and potential mechanisms of cinobufotalin (CB), a traditional Chinese medicine (TCM), on bone loss.DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis. Micro-CT, histological and morphological analysis were applied for the bone protective detection of CB, and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells (hBMMSCs) were also investigated. The underlying mechanism was verified using qRT-PCR, Western blot (WB), immunofluorescence (IF), etc. RESULTS: A safe concentration (0.25 mg/kg in vivo, 0.05 μM in vitro) of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs. Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation, further regulating the expression of osteogenesis-associated factors, and ultimately promoting osteogenesis.Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss, further promoting osteogenic differentiation/function of hBMMSCs, with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.© 2023 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.LuDa-ZhuangDZDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.ZengLi-JunLJDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.LiYangYDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.GuRan-LiRLDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.HuMeng-LongMLDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.ZhangPingPDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.YuPengPNational Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China.ZhangXiaoXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.XieZheng-WeiZWPeking University International Cancer Institute, Peking University Health Science Center, Peking University, Beijing, China.LiuHaoH0000-0003-0977-5884Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.ZhouYong-ShengYSDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.National Center of Stomatology, Beijing, China.National Clinical Research Center for Oral Diseases, Beijing, China.Beijing Key Laboratory of Digital Stomatology, Beijing, China.Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.engL222145Beijing Natural Science FoundationL222030Beijing Natural Science FoundationPKU2022XGK008Emerging Engineering Interdisciplinary Project and the Fundamental Research Funds for the Central UniversitiesBMU2022PY010Peking University Medicine Fund of Fostering Young Scholars' Scientific & Technological InnovationJournal Article20231128
United StatesAnimal Model Exp Med1017262922576-20950BufanolidesL0QBZ37386cinobufotalin0Bone Morphogenetic Proteins0Smad ProteinsIMAnimalsBufanolidespharmacologyWnt Signaling Pathwaydrug effectsFemaleOvariectomyadverse effectsMiceOsteoporosisprevention & controlHumansBone Morphogenetic ProteinsmetabolismOsteogenesisdrug effectsSmad ProteinsmetabolismMesenchymal Stem Cellsdrug effectsmetabolismCell Differentiationdrug effectsBMPs/SMADWnt/β‐catenin signaling pathwaysbone losscinobufotalinhBMMSCsosteogenesisosteoporosisAuthors declare that there are no conflicts of interest regarding the publication of this article.202383020231016202478642202311286422023112834720231128ppublish38013618PMC1122809010.1002/ame2.12359Bouvard B, Annweiler C, Legrand E. Osteoporosis in older adults. 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2227-90591182023Aug03BiomedicinesBiomedicinesBHLHE40 Maintains the Stemness of PαS Cells In Vitro by Targeting Zbp1 through the Wnt/β-Catenin Signaling Pathway.219010.3390/biomedicines11082190Primary bone mesenchymal stem cells (BMSCs) gradually lose stemness during in vitro expansion, which significantly affects the cell therapeutic effects. Here, we chose murine PαS (SCA-1+PDGFRα+CD45-TER119-) cells as representative of BMSCs and aimed to explore the premium culture conditions for PαS cells. Freshly isolated (fresh) PαS cells were obtained from the limbs of C57/6N mice by fluorescence-activated cell sorting (FACS). We investigated the differences in the stemness of PαS cells by proliferation, differentiation, and stemness markers in vitro and by ectopic osteogenesis and chondrogenesis ability in vivo, as well as the changes in the stemness of PαS cells during expansion in vitro. Gain- and loss-of-function experiments were applied to investigate the critical role and underlying mechanism of the basic helix-loop-helix family member E40 (BHLHE40) in maintaining the stemness of PαS cells. The stemness of fresh PαS cells representative in vivo was superior to that of passage 0 (P0) PαS cells in vitro. The stemness of PαS cells in vitro decreased gradually from P0 to passage 4 (P4). Moreover, BHLHE40 plays a critical role in regulating the stemness of PαS cells during in vitro expansion. Mechanically, BHLHE40 regulates the stemness of PαS cells by targeting Zbp1 through the Wnt/β-catenin signaling pathway. This work confirms that BHLHE40 is a critical factor for regulating the stemness of PαS cells during expansion in vitro and may provide significant indications in the exploration of premium culture conditions for PαS cells.HuMenglongMDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.TianYuemingY0000-0002-7027-7836Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.LiuXuenanXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.GuoQianQDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.LuDazhuangDDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.WangXuX0000-0002-8466-0828Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.LvLongweiLDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.ZhangXiaoXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.LiuYunsongY0000-0001-8364-1898Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.ZhouYongshengY0000-0002-4332-0878Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.ZhangPingPDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.eng81970911National Natural Science Foundation of China81930026National Natural Science Foundation of ChinaJournal Article20230803
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1422-006724112023Jun05International journal of molecular sciencesInt J Mol SciZIM1 Combined with Hydrogel Inhibits Senescence of Primary PαS Cells during In Vitro Expansion.976610.3390/ijms24119766Bone marrow stem cells (BMSCs) are a promising source of seed cells in bone tissue engineering, which needs a great quantity of cells. Cell senescence occurs as they are passaged, which could affect the therapeutic effects of cells. Therefore, this study aims to explore the transcriptomic differences among the uncultured and passaged cells, finding a practical target gene for anti-aging. We sorted PαS (PDGFR-α+SCA-1+CD45-TER119-) cells as BMSCs by flow cytometry analysis. The changes in cellular senescence phenotype (Counting Kit-8 (CCK-8) assay, reactive oxygen species (ROS) test, senescence-associated β-galactosidase (SA-β-Gal) activity staining, expression of aging-related genes, telomere-related changes and in vivo differentiation potential) and associated transcriptional alterations during three important cell culture processes (in vivo, first adherence in vitro, first passage, and serial passage in vitro) were studied. Overexpression plasmids of potential target genes were made and examed. Gelatin methacryloyl (GelMA) was applied to explore the anti-aging effects combined with the target gene. Aging-related genes and ROS levels increased, telomerase activity and average telomere length decreased, and SA-β-Gal activities increased as cells were passaged. RNA-seq offered that imprinted zinc-finger gene 1 (Zim1) played a critical role in anti-aging during cell culture. Further, Zim1 combined with GelMA reduced the expression of P16/P53 and ROS levels with doubled telomerase activities. Few SA-β-Gal positive cells were found in the above state. These effects are achieved at least by the activation of Wnt/β-catenin signaling through the regulation of Wnt2. The combined application of Zim1 and hydrogel could inhibit the senescence of BMSCs during in vitro expansion, which may benefit clinical application.TianYuemingY0000-0002-7027-7836Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.HuMenglongMDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.LiuXuenanXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.WangXuXDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.LuDazhuangDDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.LiZhengZDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.LiuYunsongY0000-0001-8364-1898Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.ZhangPingPDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.ZhouYongshengY0000-0002-4332-0878Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Center for Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.eng7202233Beijing Natural Science Foundation81970911National Natural Science Foundation of China81930026National Natural Science Foundation of ChinaJournal Article20230605
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1552-498110942021AprJournal of biomedical materials research. Part B, Applied biomaterialsJ Biomed Mater Res B Appl BiomaterEvaluation of osteogenic and antibacterial properties of strontium/silver-containing porous TiO2 coatings prepared by micro-arc oxidation.505516505-51610.1002/jbm.b.34719Ti and Ti alloys are bioinert materials and two frequent problems associated with them are bacterial infection and lack of osteogenic potential for rapid bone integration. To overcome the problems, the present study incorporated strontium (Sr) and silver (Ag) simultaneously into porous TiO2 coatings through a single-step technique, micro-arc oxidation (MAO). Incorporation of Sr and Ag brought no significant changes to coating micromorphology and physicochemical properties, but endowed TiO2 coatings with both strong antibacterial activity and osteogenic ability. Antibacterial activity increased with Ag contents in the coatings. When Ag content reached 0.58 wt%, the coating showed both excellent short-term (100.0%) and long-term (77.6%) antibacterial activities. Sr/Ag-containing coatings with 18.23 wt% Sr and 0.58 wt% Ag also presented good cytocompatibility for preosteoblast adhesion and proliferation, and promoted preosteoblast osteogenic differentiation both short-termly and long-termly. However, higher Ag content (1.29 wt%) showed toxic effects to preosteoblasts. In summary, MAO is a simple and effective way to incorporate Sr and Ag into porous TiO2 coatings and Sr/Ag-containing TiO2 coating with 18.5 wt% Sr and 0.58 wt% Ag has both good osteogenic activity and strong antibacterial capability short-termly and long-termly. Therefore, such coatings are valuable for clinical application to strengthen osseointegration and long-term high quality use of titanum implants.© 2020 Wiley Periodicals LLC.ZhangYang-YangYYDepartment of Oral and Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan, Hebei, China.ZhuYeYDepartment of Oral and Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan, Hebei, China.LuDa-ZhuangDZDepartment of Oral and Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan, Hebei, China.DongWeiWDepartment of Oral and Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan, Hebei, China.BiWen-JuanWJDepartment of Oral and Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan, Hebei, China.FengXiao-JieXJDepartment of Oral and Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan, Hebei, China.WenLi-MingLMDepartment of Oral and Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan, Hebei, China.SunHongHDepartment of Pathology, college of basic medicine, North China University of Science and Technology, Tangshan, Hebei, China.QiMeng-ChunMC0000-0001-5681-5282Department of Oral and Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan, Hebei, China.engJournal ArticleResearch Support, Non-U.S. Gov't20200831
United StatesJ Biomed Mater Res B Appl Biomater1012342381552-49730Anti-Bacterial Agents0Coated Materials, Biocompatible15FIX9V2JPtitanium dioxide3M4G523W1GSilverD1JT611TNETitaniumYZS2RPE8LEStrontiumIMAnti-Bacterial AgentspharmacologyCell Adhesiondrug effectsCell Divisiondrug effectsCell LineChemical PhenomenaCoated Materials, BiocompatiblepharmacologyHumansHydrophobic and Hydrophilic InteractionsMicrobial Sensitivity TestsOsteoblastsdrug effectsultrastructureOsteogenesisdrug effectsOxidation-ReductionPorositySilverpharmacologyStaphylococcus aureusdrug effectsStrontiumpharmacologySurface PropertiesTitaniumpharmacologyX-Ray Diffractionantibacterial propertymicro-arc oxidationosteogenic abilitysilverstronium202021820208112020818202091602022216020209160ppublish3286533710.1002/jbm.b.34719REFERENCESLi YH, Yang C, Zhao H, Qu S, Li X, Li Y. New developments of Ti-based alloys for biomedical applications. Materials. 2014;7(3):1709-1800.Niinomi M. 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1552-498110882020NovJournal of biomedical materials research. Part B, Applied biomaterialsJ Biomed Mater Res B Appl BiomaterEffectiveness of strontium-doped brushite, bovine-derived hydroxyapatite and synthetic hydroxyapatite in rabbit sinus augmentation with simultaneous implant installation.340234123402-341210.1002/jbm.b.34675Various bone substitutes have been applied in sinus augmentation (SA) to overcome insufficient bone height at the posterior maxilla region caused by pneumatized sinus and severe alveolar bone resorption after teeth loss. However, their effectiveness in SA needs to be further elucidated. In this study, strontium-doped brushite (Sr-DCPD), a new bone substitute, together with bovine-derived hydroxyapatite (bHA) and synthetic hydroxyapatite (sHA) was used in rabbit maxillary SA with simultaneous implant installation. The sinus space-keeping capacity, resorption rate, osteoconductivity, and mechanical properties of regenerated bone, were evaluated by micro-computed tomography (CT), histological analysis, and mechanical testing. Sr-DCPD exhibited the best osteoconductivity and new bone formation (<4 weeks), but its final bone regeneration and removal torque of implants at week 12 were the lowest, mainly due to its poor space-keeping capacity and fast resorption. bHA exhibited the best space-keeping capacity and slowest resorption rate, but relative lower final bone volume and mechanical properties, while sHA showed good space-keeping capacity, slower resorption rate, and the best final bone formation and mechanical properties. sHA was most effective for SA and bHA was also an acceptable bone substitute; however, Sr-DCPD was least effective and not suitable in SA by itself.© 2020 Wiley Periodicals LLC.LuDa-ZhuangDZDepartment of Oral & Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan City, Hebei Province, China.ZhangYan-BoYBDepartment of stomatology, Affiliated hospital of Chengde Medical College, Chengde City, Hebei Province, China.DongWeiWDepartment of Oral & Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan City, Hebei Province, China.BiWen-JuanWJDepartment of Oral & Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan City, Hebei Province, China.FengXiao-JieXJDepartment of Oral & Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan City, Hebei Province, China.WenLi-MingLMDepartment of Oral & Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan City, Hebei Province, China.SunHongHDepartment of pathology, college of basic medicine, North China University of Science and Technology, Tangshan City, Hebei Province, China.ChenHuiHDepartment of Oral & Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan City, Hebei Province, China.ZangLu-YangLYDepartment of Endocrinology (Section 1), Tangshan Gongren Hospital, Tangshan City, Hebei Province, China.QiMeng-ChunMC0000-0001-5681-5282Department of Oral & Maxillofacial Surgery, College of stomatology, North China University of Science and Technology, Tangshan City, Hebei Province, China.engJournal ArticleResearch Support, Non-U.S. Gov't20200703
United StatesJ Biomed Mater Res B Appl Biomater1012342381552-49730Biocompatible Materials0Bone Substitutes0Calcium Phosphates91D9GV0Z28DurapatiteO7TSZ97GEPcalcium phosphate, dibasic, dihydrateYZS2RPE8LEStrontiumIMAnimalsBiocompatible MaterialsBone ConductionBone Regenerationdrug effectsBone ResorptionBone SubstituteschemistryCalcium PhosphateschemistrypharmacologyCattleDurapatitechemistrypharmacologyHumansMaleMaxillary SinussurgeryMechanical PhenomenaMiddle AgedOsteogenesisdrug effectsProstheses and ImplantsRabbitsSinus Floor AugmentationmethodsStrontiumchemistrypharmacologyX-Ray Microtomographybovine-derived hydroxyapatitedental implantssinus augmentationstrontium-doped brushitesynthetic hydroxyapatite20202132020652020692020746020211196020207460ppublish3261810010.1002/jbm.b.34675REFERENCESBaier, M., Staudt, P., Klein, R., Sommer, U., Wenz, R., Grafe, I., … Kasperk, C. (2013). 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In vitro and in vivo evaluation of strontium-containing nanostructured carbonated hydroxyapatite/sodium alginate for sinus lift in rabbits. Journal of Biomedical Materials Research. Part B, Applied Biomaterials, 104, 274-282.Wallace, S. S., & Froum, S. J. (2003). Effect of maxillary sinus augmentation on the survival of endosseous dental implants. A systematic review. Annals of Periodontology, 8, 328-343.Wanschitz, F., Figl, M., Wagner, A., & Rolf, E. (2006). Measurement of volume changes after sinus floor augmentation with a phycogenic hydroxyapatite. The International Journal of Oral & Maxillofacial Implants, 21, 433-438.Xia, L., Xu, Y., Wei, J., Zeng, D., Ye, D., Liu, C., … Jiang, X. (2011). Maxillary sinus floor elevation using a tissue-engineered bone with rhBMP-2-loaded porous calcium phosphate cement scaffold and bone marrow stromal cells in rabbits. Cells, Tissues, Organs, 194, 481-493.Yildirim, M., Spiekermann, H., Biesterfeld, S., & Edelhoff, D. (2000). Maxillary sinus augmentation using xenogenic bone substitute material bio-Oss in combination with venous blood. A histologic and histomorphometric study in humans. Clinical Oral Implants Research, 11, 217-229.321733492021052720210527
1872-80575082020May15Molecular and cellular endocrinologyMol Cell EndocrinolCaMKII(δ) regulates osteoclastogenesis through ERK, JNK, and p38 MAPKs and CREB signalling pathway.11079111079110.1016/j.mce.2020.110791S0303-7207(20)30091-5Calcium/calmodulin-dependent protein kinases (CaMKs) are a group of important molecules mediating calcium signal transmission and have been proved to participate in osteoclastogenesis regulation. CaMKII, a subtype of CaMKs is expressed during osteoclast differentiation, but its role in osteoclastogenesis regulation remains controversial. In the present study, we identified that both mRNA and protein levels of CaMKII (δ) were upregulated in a time-dependent manner during osteoclast differentiation. CaMKII (δ) gene silencing significantly inhibited osteoclast formation, bone resorption, and expression of osteoclast-related genes, including nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and c-Src. Furthermore, CaMKII (δ) gene silencing downregulated phosphorylation of mitogen-activated protein kinases (MAPKs), including JNK, ERK, and p38, which were transiently activated by RANKL. Specific inhibitors of ERK, JNK, and p38 also markedly inhibited expression of osteoclast-related genes, osteoclast formation, and bone resorption like CaMKII (δ) gene silencing. Additionally, CaMKII (δ) gene silencing also suppressed RANKL-triggered CREB phosphorylation. Collectively, these data demonstrate the important role of CaMKII (δ) in osteoclastogenesis regulation through JNK, ERK, and p38 MAPKs and CREB pathway.Copyright © 2020 Elsevier B.V. All rights reserved.LuDa-ZhuangDZDepartment of Oral & Maxillofacial Surgery, College of Stomatology, North China University of Science and Technology, 21, Bohai Road, District of Caofeidian, Tangshan City, 063210, Hebei Province, PR China.DongWeiWDepartment of Oral & Maxillofacial Surgery, College of Stomatology, North China University of Science and Technology, 21, Bohai Road, District of Caofeidian, Tangshan City, 063210, Hebei Province, PR China.FengXiao-JieXJDepartment of Oral & Maxillofacial Surgery, College of Stomatology, North China University of Science and Technology, 21, Bohai Road, District of Caofeidian, Tangshan City, 063210, Hebei Province, PR China.ChenHuiHDepartment of Oral & Maxillofacial Surgery, Affiliated Hospital of North China University of Science and Technology, Tangshan City, 063000, Hebei Province, PR China.LiuJuan-JuanJJDepartment of Oral & Maxillofacial Surgery, College of Stomatology, North China University of Science and Technology, 21, Bohai Road, District of Caofeidian, Tangshan City, 063210, Hebei Province, PR China.WangHuiHDepartment of Oral & Maxillofacial Surgery, College of Stomatology, North China University of Science and Technology, 21, Bohai Road, District of Caofeidian, Tangshan City, 063210, Hebei Province, PR China.ZangLu-YangLYDepartment of Endocrinology (Section 1), Tangshan Gongren Hospital, Tangshan City, 063000, Hebei Province, PR China.QiMeng-ChunMCDepartment of Oral & Maxillofacial Surgery, College of Stomatology, North China University of Science and Technology, 21, Bohai Road, District of Caofeidian, Tangshan City, 063210, Hebei Province, PR China. Electronic address: qimengchun@163.com.engJournal ArticleResearch Support, Non-U.S. Gov't20200312
IrelandMol Cell Endocrinol75008440303-72070Cyclic AMP Response Element-Binding Protein0Protein Kinase Inhibitors0RANK LigandEC 2.7.11.17Calcium-Calmodulin-Dependent Protein Kinase Type 2EC 2.7.11.24Extracellular Signal-Regulated MAP KinasesEC 2.7.11.24JNK Mitogen-Activated Protein KinasesEC 2.7.11.24p38 Mitogen-Activated Protein KinasesEC 3.1.3.2Tartrate-Resistant Acid PhosphataseIMAnimalsBone ResorptiongeneticspathologyCalcium-Calmodulin-Dependent Protein Kinase Type 2metabolismCell Differentiationdrug effectsCyclic AMP Response Element-Binding ProteinmetabolismDown-Regulationdrug effectsgeneticsExtracellular Signal-Regulated MAP KinasesmetabolismGene Silencingdrug effectsJNK Mitogen-Activated Protein KinasesmetabolismMiceOsteoclastscytologydrug effectsmetabolismOsteogenesisdrug effectsPhosphorylationdrug effectsProtein Kinase InhibitorspharmacologyRANK LigandpharmacologyRAW 264.7 CellsSignal Transductiondrug effectsTartrate-Resistant Acid PhosphatasemetabolismTime Factorsp38 Mitogen-Activated Protein KinasesmetabolismCalcium/calmodulin-dependent protein kinasesExtracellular signal-regulated kinasesOsteoclastc-Jun amino-terminal kinasescAMP response element binding proteinp38Declaration of competing interest The authors declare no conflicts of interest related to this study.2019992020122020310202031760202152860202031760ppublish3217334910.1016/j.mce.2020.110791S0303-7207(20)30091-5trying2...
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M2 Macrophages Guide Periosteal Stromal Cell Recruitment and Initiate Bone Injury Regeneration.
Dazhuang Lu Yingfei Zhang Shimin Liang Yang Li Jia Qing

Biomedicines

May 2024

The periosteum plays a critical role in bone repair and is significantly influenced by the surrounding immune microenvironment. In this study, we employed 10× single-cell RNA sequencing to create a detailed cellular atlas of the swine cranial periosteum, highlighting the cellular dynamics and interactions essential for cranial bone injury repair. We noted that such injuries lead to an increase in M2 macrophages, which are key in modulating the periosteum's immune response and driving the bone regeneration process.

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UBE2C orchestrates bone formation through stabilization of SMAD1/5.
Hui Zhang Yangge Du Dazhuang Lu Xu Wang Yang Li

Bone

October 2024

While previous studies have demonstrated the role of ubiquitin-conjugating enzyme 2C (UBE2C) in promoting β-cell proliferation and cancer cell lineage expansion, its specific function and mechanism in bone marrow mesenchymal stem/stromal cells (BMSCs) growth and differentiation remain poorly understood. Our findings indicate that mice with conditional Ube2c deletions in BMSCs and osteoblasts exhibit reduced skeletal bone mass and impaired bone repair. A significant reduction in the proliferative capacity of BMSCs was observed in conditional Ube2c knockout mice, with no effect on apoptosis.

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Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways.
Da-Zhuang Lu Li-Jun Zeng Yang Li Ran-Li Gu Meng-Long Hu

Animal Model Exp Med

June 2024

Article Synopsis
  • Osteoporosis is a bone disease that makes bones weak, and some medicines for it can cause side effects.
  • The study tested a traditional Chinese medicine called cinobufotalin (CB) to see if it can help prevent bone loss.
  • Results showed that CB can help keep bones strong and work well with certain biological pathways to improve the growth of bone cells.
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BHLHE40 Maintains the Stemness of PαS Cells In Vitro by Targeting through the Wnt/β-Catenin Signaling Pathway.
Menglong Hu Yueming Tian Xuenan Liu Qian Guo Dazhuang Lu

Biomedicines

August 2023

Primary bone mesenchymal stem cells (BMSCs) gradually lose stemness during in vitro expansion, which significantly affects the cell therapeutic effects. Here, we chose murine PαS (SCA-1PDGFRαCD45TER119) cells as representative of BMSCs and aimed to explore the premium culture conditions for PαS cells. Freshly isolated (fresh) PαS cells were obtained from the limbs of C57/6N mice by fluorescence-activated cell sorting (FACS).

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ZIM1 Combined with Hydrogel Inhibits Senescence of Primary PαS Cells during In Vitro Expansion.
Yueming Tian Menglong Hu Xuenan Liu Xu Wang Dazhuang Lu

Int J Mol Sci

June 2023

Bone marrow stem cells (BMSCs) are a promising source of seed cells in bone tissue engineering, which needs a great quantity of cells. Cell senescence occurs as they are passaged, which could affect the therapeutic effects of cells. Therefore, this study aims to explore the transcriptomic differences among the uncultured and passaged cells, finding a practical target gene for anti-aging.

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Evaluation of osteogenic and antibacterial properties of strontium/silver-containing porous TiO coatings prepared by micro-arc oxidation.
Yang-Yang Zhang Ye Zhu Da-Zhuang Lu Wei Dong Wen-Juan Bi

J Biomed Mater Res B Appl Biomater

April 2021

Ti and Ti alloys are bioinert materials and two frequent problems associated with them are bacterial infection and lack of osteogenic potential for rapid bone integration. To overcome the problems, the present study incorporated strontium (Sr) and silver (Ag) simultaneously into porous TiO coatings through a single-step technique, micro-arc oxidation (MAO). Incorporation of Sr and Ag brought no significant changes to coating micromorphology and physicochemical properties, but endowed TiO coatings with both strong antibacterial activity and osteogenic ability.

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Effectiveness of strontium-doped brushite, bovine-derived hydroxyapatite and synthetic hydroxyapatite in rabbit sinus augmentation with simultaneous implant installation.
Da-Zhuang Lu Yan-Bo Zhang Wei Dong Wen-Juan Bi Xiao-Jie Feng Lu-Yang Zang

J Biomed Mater Res B Appl Biomater

November 2020

Various bone substitutes have been applied in sinus augmentation (SA) to overcome insufficient bone height at the posterior maxilla region caused by pneumatized sinus and severe alveolar bone resorption after teeth loss. However, their effectiveness in SA needs to be further elucidated. In this study, strontium-doped brushite (Sr-DCPD), a new bone substitute, together with bovine-derived hydroxyapatite (bHA) and synthetic hydroxyapatite (sHA) was used in rabbit maxillary SA with simultaneous implant installation.

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CaMKII(δ) regulates osteoclastogenesis through ERK, JNK, and p38 MAPKs and CREB signalling pathway.
Da-Zhuang Lu Wei Dong Xiao-Jie Feng Hui Chen Juan-Juan Liu Lu-Yang Zang

Mol Cell Endocrinol

May 2020

Calcium/calmodulin-dependent protein kinases (CaMKs) are a group of important molecules mediating calcium signal transmission and have been proved to participate in osteoclastogenesis regulation. CaMKII, a subtype of CaMKs is expressed during osteoclast differentiation, but its role in osteoclastogenesis regulation remains controversial. In the present study, we identified that both mRNA and protein levels of CaMKII (δ) were upregulated in a time-dependent manner during osteoclast differentiation.

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