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Rat adipose-derived stromal cells expressing BMP4 induce ectopic bone formation in vitro and in vivo

Acta Pharmacologica Sinica 2006年第12期27卷 1608-1615页

作者： Lin LIN~2 Xin FU~2 Xin ZHANG~2 Lian-xu CHEN~2 Ji-ying ZHANG~2 Chang-long YU~(2,4)Kang-tao MA~3 Chun-yan ZHOU~(3,4)2 Institute of Sports Medicine,Peking University Third Hospital,Beijing 100083,China 3 Department of Biochemistry and Molecular Biology,Peking University School of Basic Medical Science,Beijing 100083,China Institute of Sports Medicine Peking University Third Hospital Beijing China Department of Biochemistry and Molecular Biology Peking University School of Basic Medical Science Beijing China

Aim:bone morphogenetic protein 4(BMP4)is one of the main local contributingfactors in callus formation in the early phase of fracture ***-derivedstromal cells(ADSC)are multipotent *** present study was conducted toinvestigate the osteogenic potential of ADSC when exposed to adenovirus con-taining BMP4 cDNA(Ad-BMP4).Methods:ADSC were harvested from Sprague-Dawley *** exposure to Ad-BMP4,ADSC were assessed by alkaline phos-phatase activity(ALP)assay,RT-PCR and yon Kossa ***4 expressionwas assessed by RT-PCR,immunofluorescence and Western blot analysis,ADSCtransduced with Ad-BMP4 were directly injected into the hind limb muscles ofathyrnic *** Ad-EGFP(enhanced green fluorescence protein)served *** animals were examined by X-ray film and histological ***:The expression of BMP4 was confirmed at both mRNA and protein *** expression of the osteoblastic gene,ALP activity and yon Kossa stainingconfirmed that ADSC transduced with Ad-BMP4 underwent rapid and markedosteoblast differentiation,whereas ADSC transduced with Ad-EGFP and cells leftalone displayed no osteogenic differentiation.X-ray and histological examinationconfirmed new bone formation in athymic mice transplanted with ADSC trans-duced with ***:Our data demonstrated successful osteo-genic differentiation of ADSC transduced with Ad-BMP4 in vitro and in *** may be an ideal source of mesenchyme lineage stem cells for gene therapyand tissue engineering.

关键词： adipose-derived stromal cells BMP4 gene therapy bone formation

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The effect of carbon nanotubes on osteogenic functions of adipose-derived mesenchymal stem cells in vitro and bone formation in vivo compared with that of nano-hydroxyapatite and the possible mechanism

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Bioactive Materials 2021年第2期6卷 333-345页

作者： Zhipo Du Xinxing Feng Guangxiu Cao Zhending She Rongwei Tan Katerina E.Aifantis Ruihong Zhang Xiaoming Li Department of Orthopedics The Fourth Central Hospital of Baoding CityBaoding072350China Endocrinology and Cardiovascular Disease Centre Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical EngineeringBeihang UniversityBeijing100083China Beijing Advanced Innovation Center for Biomedical Engineering Beihang UniversityBeijing100083China Guangdong Engineering Research Center of Implantable Medical Polymer Shenzhen Lando Biomaterials Co.Ltd.Shenzhen518107China Department of Mechanical and Aerospace Engineering University of FloridaGainesvilleFL32611USA Department of Research and Teaching The Fourth Central Hospital of Baoding CityBaoding072350China

It has been well recognized that the development and use of artificial materials with high osteogenic ability is one of the most promising means to replace bone grafting that has exhibited various negative *** biomimetic features and unique physiochemical properties of nanomaterials play important roles in stimulating cellular functions and guiding tissue *** efficacy degree of some nanomaterials to promote specific tissue formation is still not *** hereby comparatively studied the osteogenic ability of our treated multiwalled carbon nanotubes(MCNTs)and the main inorganic mineral component of natural bone,nano-hydroxyapatite(nHA)in the same system,and tried to tell the related *** vitro culture of human adiposederived mesenchymal stem cells(HASCs)on the MCNTs and nHA demonstrated that although there was no significant difference in the cell adhesion amount between on the MCNTs and nHA,the cell attachment strength and proliferation on the MCNTs were *** importantly,the MCNTs could induce osteogenic differentiation of the HASCs better than the nHA,the possible mechanism of which was found to be that the MCNTs could activate Notch involved signaling pathways by concentrating more proteins,including specific bone-inducing ***,the MCNTs could induce ectopic bone formation in vivo while the nHA could not,which might be because MCNTs could stimulate inducible cells in tissues to form inductive bone better than nHA by concentrating more proteins including specific bone-inducing ones secreted from M2 ***,MCNTs might be more effective materials for accelerating bone formation even than nHA.

关键词： Multi-walled carbon nanotubes(MCNTs) bone repair material Protein adsorption Osteogenic differentiation bone formation

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Intracystic negative pressure may promote bone formation around jaw cysts

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上海口腔医学 2011年第2期20卷 217-218页

作者：赵熠刘冰 Department of Prosthodontics School and Hospital of StomatologyWuhan University Department of Oral and Maxillofacial Surgery School and Hospital of StomatologyWuhan University

The growth and enlargement of jaw cysts are associated with raised intracystic pressure and bone resorption surrounding the *** major bone-resorbing cells are the *** are acting under the influence of local bone-resorbing factors: prostaglandins,proteinases and *** was found that positive pressure enhanced the expression of IL-1αmRNA and protein in epithelial cells of odontogenic keratocyst,and increased the secretion of matrix metalloproteinase and PGE2 in a co-culture of odontogenic keratocyst fibroblasts and epithelial ***,the signal intensities for IL-1α mRNA and protein in the epithelium were significantly decreased after marsupialization which relived intracystic *** study indicated that intermittent negative pressure could promote osteogenesis in human bone marrow-derived stroma cells(BMSCs) in *** propose a hypothesis that bone formation around the cyst of the jaws would be stimulated by intracystic negative pressure.

关键词： Jaw cysts bone formation Negative pressure

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Role of Epithelium Sodium Channel in bone formation

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Chinese Medical Journal 2016年第5期129卷 594-600页

作者： Ruo-Yu Wang Shu-Hua Yang Wei-Hua Xu Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430022 China

Objective：To review the recent developments in the mechanisms of epithelium sodium channels （ENaCs） induced bone formation and *** Sources：Studies written in English or Chinese were searched using Medline,PubMed and the index of Chinese-language literature with time restriction from 2005 to *** included ENaC,bone,bone formation,osteonecrosis,estrogen,and *** from published articles about the structure of ENaC,mechanism of ENaC in bone formation in recent domestic and foreign literature were *** Selection：Abstract and full text of all studies were required to *** those were not accessible and those did not focus on the keywords were ***：ENaCs are tripolymer ion channels which are assembled from homologous α,β,and γ *** structure of ENaCs suggests that ENaC has a central ion-channel located in the central symmetry axis of the three *** are protease sensitive channels whose iron-channel activity is regulated by the proteolytic *** opening probability of ENaCs is regulated by proteinases,mechanical force,and shear *** molecules are involved in regulation of ENaCs in bone formation,including nitride oxide synthases,voltage-sensitive calcium channels,and ***：The pathway of ENaC involved in shear stress has an effect on stimulating osteoblasts even bone formation by estrogen interference.

关键词： bone formation Epithelium Sodium Channel Estrogen Osteoblasts Shear Stress

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Low-intensity pulsed ultrasound prompts tissue-engineered bone formation after implantation surgery

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Chinese Medical Journal 2014年第4期127卷 669-674页

作者： Wang Juyong Wang Juqiang Asou Yoshinori Paul Fu Shen Huiliang Chen Jiani Sotome Shinichi Department of Orthopaedic Surgery Xuanwu Hospital Capital Medical University Beijing 100053 China Department of Orthopaedics First Hospital of China Medical University Shenyang Liaoning 110001 China Department of Orthopaedic Surgery Graduate School Tokyo Medical and Dental University Tokyo 1138519 Japan Department of Neurological Surgery Wayne State University School of Medicine Detroit MI 48201 USA Department of Orthopaedic Surgery Graduate School Tokyo Medical and Dental University Tokyo 1138519 Japan COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and bone Tokyo Medical and Dental University Bunkyo-ku Tokyo 1138519 Japan

Background A practical problem impeding clinical translation is the limited bone formation seen in artificial bone ***-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds,enhanced production of bone marrow cells,and improved tissue-engineered bone *** goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells （BMSCs）.Methods BMSCs/β-tricalcium phosphate （β-TCP） composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound （LIPUS） treatment group and a control *** implants were harvested at 5,10,25,and 50 days after *** samples were then biomechanically tested and analyzed for alkaline phosphate （ALP） activity and osteocalcin （OCN） content and were also observed by light *** The levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control *** analysis revealed a greater degree of soft tissue repair,increased blood flow,better angiogenesis,and more extensive bone formation in the LIPUS groups than in the *** significant difference in the compressive strength was found between the two *** LIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/β3-TCP composites.

关键词： β-tricalcium phosphate low-intensity pulsed ultrasound marrow stromal cells bone formation

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Osteoblast-derived extracellular vesicles exert bone formation effects by WIF1-mediated regulation of mitophagy

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医学+（英文） 2024年第2期1卷 48-63页

作者： Yuyuan Gu Jing Zhao Jian Wang Yingying Jiang Yingying Jing Ke Xu Jiacan Su Institute of Translational Medicine Shanghai UniversityShanghai 200444China Orgpnoid Research Center Shanghai UniversityShanghai 200444China School of Medicine Shanghai UniversityShanghai 200444China Wenzhou Institute of Shanghai University Wenzhou 325000 China Department of Orthopaedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

Background:Osteoporosis arises mainly from an imbalance in bone remodeling,characterized by the impaired ability of osteoblasts(OBs)to form new bone.A sig-nificant challenge remains in identifying and validating key genes involved in os-teogenic differentiation to develop effective ***:The regulatory role of WIF1 in osteogenic differentiation stages was in-vestigated using Western blot and quantitative polymerase chain reaction assays to measure the expression levels of osteogenic-related genes in MC3T3-E1 *** of OBs was assessed through alizarin red S(ARS)and alkaline phos-phatase(ALP)staining *** explore the relationship with mitophagy,RNA se-quencing was performed to examine the effects of Wif1 overexpression on genes re-lated to osteogenic differentiation and mitophagy ***,histological staining and micro-computed tomography were conducted on ovar-iectomized(OVX)mice treated with Wif1-overexpressing OB-derived extracellular vesicles(EVs)to evaluate their impact on bone loss and osteogenic differentiation in bone marrow stromal cells(BMSCs).Results:Wif1 was identified as a crucial marker for late-stage osteogenic differentia-tion,playing a role in regulating mitophagy to release functional *** vitro ana-lyses showed that Wif1 overexpression accelerated osteogenic differentiation by ac-tivating genes related to late-stage osteogenic differentiation and mitophagy *** vivo experiments demonstrated that administering Wif1-overexpressing OB-derived EVs to OVX mice partially reversed bone loss and countered the sup-pression of osteogenic differentiation in ***:Our findings shed light on the molecular mechanism of Wif1 in osteogenic differentiation and suggested the therapeutic efficacy of Wif1-overexpressing OB-derived EVs in osteoporosis.

关键词： WIF1 Osteoporosis Osteoblast Mitophagy Extracellular vesicle bone formation

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Mesenchymal stem cell sheet transplantation combined with locally released simvastatin enhances bone formation in a rat tibia osteotomy model

Mesenchymal stem cell sheet transplantation combined with lo...

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2012年浙江省骨科学术年会

作者： Jianwei Wang Yiying Q Tengfei Zhao Weiqi Yan Kan Xu Zhongli Shi Department of Orthopedic Surgery the Second Affiliated Hospital School of Medicine Zhejiang University

Nonunion of fractured bones is a common clinical problem for orthopedic surgeons. This study aimed to investigate the effects of simvastatin locally applied from calcium sulphate (CS) combined with mesenchymal stem cell (MSC) sheet on fracture healing. In vitro, the proliferation and differentiation of rat bone marrow derived MSCs stimulated by simvastatin were investigated. In vivo, an osteotomy model was made in rat tibia and fractured tibias were treated with CS, CS/simvastatin, CS/MSC sheet or simvastatin-loaded CS with MSC or untreated (control). Tibias were harvested at 2 or 8 weeks and underwent RT-PCR, X-ray, micro-CT and histological analysis. The expression levels of BMP-2, ALP, OCN, OPG and VEGF of simvastatin-induced MSCs increased with the concentrations of the simvastatin, significantly higher than those in the MSCs group. At 2 weeks, the CS/simvastatin/MSC sheet group showed significantly higher expressions of BMP-2, ALP, OCN, OPG and VEGF;more callus formation around the fracture site compared with other four groups. At 8 weeks, complete bone union was obtained in the CS/simvastatin/MSC sheet group. By contrast, new regenerated bone tissue partially bridged the gap in the CS/simvastatin group and CS/MSC sheet group;the control and CS group showed nonunion of the tibia. These results showed that both simvastatin and MSC sheet contributed to the formation of new bone and the tibia fracture was completely cured by transplantation of MSC sheet with locally applied simvastatin. Such MSC sheet with locally applied simvastatin may contribute to the treatment of fractures, nonunion bone defects in clinic.

关键词： simvastatin mesenchymal stem cells MSC sheet bone formation nonunion

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The roles of matrix vesicles in bone formation and heterotopic ossification

The roles of matrix vesicles in bone formation and heterotop...

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第八届全国医学生物化学与分子生物学第五届全国临床应用生物化学与分子生物学2013华东六省一市生物化学与分子生物学联合学术研讨会

作者： Pinglan Ge Yazhou Cui Jing Luan Xiaoyan Zhou Jinxiang Han Key Laboratory for Rare Disease Research of Shandong Province

In normal and healthy individuals,bone formation is normally limited to the specialized tissues,the skeleton and the dentition which forms through endochondral ossification or intramembranous *** these hard tissues,bone formation is tightly controlled both in growth and development and in normal adult *** contrast,heterotopic ossification is a pathological condition in which osteogenesis occurs outside of the skeleton,within soft tissues of the ***,the resulting extraskeletal bone is qualitatively normal endochondral or intramembranous bone,and develops through processes that parallel the events that occur during normal embryonic bone and skeletal formation,and also in bone regeneration during fracture *** increasing evidence supports the contention that the mechanisms of soft tissue ossification are similar to those seen in normal bone *** particular,matrix vesicles(MVs),small(20-200 nm) membrane particles,probably play a prominent role in mineral deposition and skeletal *** small particles are budded off from the plasma membrane of chondrocytes,osteoblasts,and odontoblasts prior to the onset of matrix mineralization and are released into the pre-mineralized organic *** perform specialized roles in initiating matrix mineralization,which regulate the Pi/PPi ratio in the intracellular and extracellular fluid,manage mineral nucleation for hydroxylapatite(HA),control calcium and Pi ion homeostasis,and interact with the surrounding ECM to direct HA localization and *** mechanisms involved in the ossification of mineralized tissues have been under investigation for many years and much progress has been made in this *** how matrix vesicles function in normal ossification and the evidence for their participation in pathologic ossification remains to be further researched and *** purpose of this study is to explore the mechanisms of MVs in hard tissue mineralization and then t

关键词： bone formation heterotopic ossification matrix vesicles mineralization hydroxylapatite

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Integrative analysis of bone-formation associated genes and immune cell infiltration in osteoporosis, and the prediction of active ingredients in targeted traditional Chinese medicine

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Digital Chinese Medicine 2024年第2期7卷 160-170页

作者： WANG Kai DONG Ping GUO Hongzhang Department of Orthopedics Gansu Provincial HospitalLanzhouGansu 730000China College of Traditional Chinese Medicine Inner Mongolia Medical UniversityHohhotInner Mongolia 010110China

Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)*** The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of *** R package was utilized as the analytical tool for the identification of differentially expressed *** absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were *** cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune *** Medical Database was used to screen out potential TCM herbs for the treatment of *** Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key *** Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological *** Ten genes were identified by intersecting the results from the GEO and GeneCards *** the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and

关键词： Osteoporosis bone formation Differentially expressed genes Biological information Traditional Chinese medicine(TCM) Active ingredients Molecular mechanism

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A bioactive glass functional hydrogel enhances bone augmentation via synergistic angiogenesis,self-swelling and osteogenesis

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Bioactive Materials 2023年第4期22卷 201-210页

作者： Fujian Zhao Zhen Yang Huacui Xiong Yang Yan Xiaofeng Chen Longquan Shao Stomatological Hospital Southern Medical UniversityGuangzhou510280China Department of Biomedical Engineering School of Materials Science and EngineeringSouth China University of TechnologyGuangzhou510641China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou510006China Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering Guangzhou510515China

bone augmentation materials usually cannot provide enough new bone for dental implants due to the material degradation and mucosal *** use of hydrogels with self-swelling properties may provide a higher bone augmentation,although swelling is generally considered to be a disadvantage in tissue ***,a double-crosslinked gelatin-hyaluronic acid hydrogels(GH)with self-swelling properties were ***,niobium doped bioactive glasses(NbBG)was dispersed in the hydrogel network to prepare the GH-NbBG *** composite hydrogel exhibited excellent biocompatibility and the addition of NbBG significantly improved the mechanical properties of the *** vivo results found that GH-NbBG synergistically promoted angiogenesis and increased bone augmentation by self-swelling at the early stage of *** addition,at the late stage after implantation,GH-NbBG significantly promoted new bone formation by activating RUNX2/Bglap signaling ***,this study reverses the self-swelling disadvantage of hydrogels into advantage and provides novel ideas for the application of hydrogels in bone augmentation.

关键词： Bioactive glass bone formation Osteogenesis Angiogenesis

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