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Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

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World Journal of stem cells 2024年第3期16卷 267-286页

作者： Tong Wu Fu Zheng Hong-Yi Tang Hua-Zhi Li Xin-Yu Cui Shuai Ding Duo Liu Cui-Ying Li Jiu-Hui Jiang Rui-Li Yang Department of Orthodontics Peking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China Department of Central Laboratory Peking University School and Hospital of StomatologyNational Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China

BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorp

关键词： Low-intensity pulsed ultrasound bone resorption Osteogenesis Cytoskeleton-Lamin A/C-Yes-associated protein axis bone marrow mesenchymal stem cells Orthodontic tooth movement

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The effect of Human LMP-1 gene on the expression of osteogenic gene in dog bone marrow mesenchymal stem cells

The effect of Human LMP-1 gene on the expression of osteogen...

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中华医学会第10届全国显微外科学术会议暨世界首例断肢再...

作者： Pu chao Li wei Ni wei-dong Qu yu Department of Orthopedics NanChong central Hospital

Objective To study the effect of Human LMP-1 gene on the expression of osteogenic gene in dog bone marrow mesenchymal stem cells.Methods Dog MSCs were infected by the recombinant adenovirus vector of human LMP-1.The expression of LMP-1,BMP-7,ALP and osteocalcin gene was detected by RT-PCR. Results The best efficiency can get at the most appropriate MOI 100 after Ad-LMP-1 infected BMSCs.Infected BMSCs can express mRNA and of LMP-1,expression of ALP increased,but not caused expression of BMP-7 and osteocalcin gene.Conclusion The recombinant adenoviral vector carring hLMP-1 gene can promote expression of osteogenic gene.

关键词： LIM mineralization protein-1 adenovirus bone marrow mesenchymal stem cells recombinant human bone morphogenetic protein -7 alkaline phosphatase

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Xuefuzhuyu injection induces neuronal differentiation of rat bone morrow mesenchymal stem cells

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Neural Regeneration Research 2011年第3期6卷 177-182页

作者： Yin, Yanqing Chen, Bing Ke, Junlong Mo, Wei Zou, Xinhui Liang, Yuansheng Guangdong Med Coll Affiliated Hosp Dept Neurosurg Zhanjiang 524001 Guangdong Peoples R China Guangdong Med Coll Affiliated Hosp Dept Neurol Zhanjiang 524001 Guangdong Peoples R China

The primary effective components of Xuefuzhuyu, including Rhizoma Chqanxiong, Radix Salviae Miltiorrhiae, and Radix Angelicae Sinensis, have been shown to induce the differentiation of bone marrow mesenchymal stem cells （BMMSCs） into neuronal-like cells. However, there is little available evidence on the effects of the Chinese herbal compound Xuefuzhuyu on BMMSC differentiation. The present study investigated the effects of Xuefuzhuyu on differentiation of rat BMMSCs into neuronal-like cells, and evaluated the optimal concentration for inducing differentiation. Inverted microscopy was used to observe BMMSCs induced by Xuefuzhuyu; immunocytochemistry revealed expression of the neuronal marker neuron-specific enolase surface antigen in the majority of BMMSCs following treatment with Xuefuzhuyu at concentrations of 1,3, 5 and 10 g/L. A concentration of 3 g/L resulted in highest neuron-specific enolase expression. These results suggest that BMMSCs can be induced to differentiate into neuronal-like cells with Xuefuzhuyu, and 3 g/L is the optimal inductive concentration for effective differentiation.

关键词： Xuefuzhuyu bone marrow mesenchymal stem cells neuronal-like cells neuralregeneration induction differentiation

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bone marrow mesenchymal stem cell treatment improves poststroke cerebral function recovery by regulating gut microbiota in rats

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World Journal of stem cells 2022年第8期14卷 680-683页

作者： Mohsen Sheykhhasan Naresh Poondla Research Center for Molecular Medicine Hamadan University of Medical SciencesHamadan ***Iran Department of Neurology Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States

Early intervention with bone marrow mesenchymal stem cells to change the form and function of the gut microbiota may help rats regain neurological function after a stroke.

关键词： Ischemic stroke bone marrow mesenchymal stem cells Neurological function Gut microbiota

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Deciphering the chromatin spatial organization landscapes during BMMSC differentiation

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Journal of Genetics and Genomics 2023年第4期50卷 264-275页

作者： Zhaowei Teng Yun Zhu Da Lin Qinggang Hao Qiaoning Yue Xiaochao Yu Shuo Sun Lihong Jiang Sheng Lu Department of Orthopedics The First People's Hospital of Yunnan ProvinceAffiliated Hospital of Kunming University of Science and TechnologyKunmingYunnan 650032China Key Laboratory of Yunnan Provincial Innovative Application of Traditional Chinese Medicine The First People's Hospital of Yunnan ProvinceKunmingYunnan 650032China Clinical Medical Research Center The First People's Hospital of Yunnan ProvinceKunmingYunnan 650032China The Sixth Affiliated Hospital of Kunming Medical University YuxiYunnan 653100China State Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhanHubei 430070China Center for Life Sciences School of Life SciencesYunnan UniversityKunmingYunnan 650504China

The differentiation imbalance in bone marrow mesenchymal stem cells(BMMSCs)is critical for the development of bone density diseases as the population ages.BMMSCs are precursor cells for osteoblasts and adipocytes;however,the chromatin organization landscapes during BMMSC differentiation remain elusive.In this study,we systematically delineate the four-dimensional genome and dynamic epigenetic atlas of BMMSCs by RNA sequencing,assay for transposase-accessible chromatin sequencing,and highthroughput chromosome conformation capture.The structure analyses reveal 17.5%common and28.5%-30%specific loops among BMMSCs,osteoblasts,and adipocytes.The subsequent correlation of genome-wide association studies and expression quantitative trait locus(e QTL)data with multi-omics analysis reveal 274 genes and 3634 single nucleotide polymorphisms(SNPs)associated with bone degeneration and osteoporosis(OP).We hypothesize that SNP mutations affect transcription factor(TF)binding sites,thereby affecting changes in gene expression.Furthermore,26 motifs,260 TFs,and 291SNPs are identified to affect the e QTL.Among these genes,DAAM2,TIMP2,and TMEM241 are found to be essential for diseases such as bone degeneration and OP and may serve as potential drug targets.

关键词： bone marrow mesenchymal stem cells Differentiation Hi-C ATAC-Seq Single nucleotide polymorphisms Genome-wide association studies

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Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia

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Neural Regeneration Research 2012年第10期7卷 749-755页

作者： Dong Wang Jianjun Zhang Department of Neurosurgery Tianjin Fourth Central Hospital Tianjin 300140 China

Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours （mild hypothermia）. Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells （bromodeoxyuridine-positive cells）, better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.

关键词： bone marrow mesenchymal stem cells electrophysiological function hypothermia spinal cord hemisection injury transplantation

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Muse cells decrease the neuroinflammatory response by modulating the proportion of M1 and M2 microglia in vitro

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Neural Regeneration Research 2023年第1期18卷 213-218页

作者： Xin-Yao Yin Chen-Chun Wang Pan Du Xue-Song Wang Yi-Chi Lu Yun-Wei Sun Yue-Hui Sun Yi-Man Hu Xue Chen Department of Basic Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu ProvinceChina Department of Orthopedics Affiliated Hospital of Jiangnan UniversityWuxiJiangsu ProvinceChina

Neuroinflammation hinders repair of the central nervous system(CNS).stem cell transplantation is a very promising approach for treatment of CNS injuries.However,it is difficult to select seed cells that can both facilitate nerve regeneration and improve the microenvironment in the CNS.In this study,we isolated multilineage-differentiating stress-enduring(Muse)cells from bone marrow mesenchymal stem cells.We explored the anti-inflammatory effect and mechanism of Muse cells in vitro by coculture of Muse cells with lipopolysaccharide-stimulated microglia.Our results showed that Muse cells effectively reduced the transcription and secretion of tumor necrosis factorαand interleukin-1βand increased the expression of transforming growth factor-βand interleukin-10 in microglia.In addition,Muse cells decreased the number of M1 microglia and increased the proportion of M2 microglia in an inflammatory environment more effectively than bone marrow mesenchymal stem cells.We also show that Muse cells inhibited the protein expression of toll-like receptor 4(TLR4)and myeloid differentiation primary response protein(MyD88)and inhibited the expression of the phosphorylated forms of transcription factor p65,nuclear factor(NF)-κB inhibitor alpha,and p38 mitogen-activated protein kinase(MAPK)in microglia.Therefore,we suggest Muse cells cause antineuroinflammatory effects by inhibition of the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways in microglia.Our results shed light on the function of Muse cells in relation to CNS diseases and provide insight into the selection of seed cells.

关键词： bone marrow mesenchymal stem cells central nervous system lipopolysaccharide multilineage-differentiating stress-enduring cells neuroinflammation microglia signaling pathway

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Development of bone marrow mesenchymal stem cell culture in vitro

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Chinese Medical Journal 2012年第9期125卷 1650-1655页

作者： ZHANG Li PENG Li-pan WU Nan LI Le-ping Department of Gastrointestinal Surgery Provincial Hospital Affiliated to Shandong UniversityJinanShandong 250021China

Objective To review the in vitro development of bone marrow mesenchymal stem cells culture （BM-MSC）.Data sources The data cited in this review were mainly obtained from articles listed in Medline and PubMed. The search terms were “bone marrow mesenchymal stem cell” and “cell culture”.Study selection Articles regarding the in vitro development of BM-MSCs culture, as well as the challenge of optimizing cell culture environment in two-dimensional （2D） vs. 3D.Results Improving the culture conditions increases the proliferation and reduces the differentiation. Optimal values for many culture parameters remain to be identified. Expansion of BM-MSCs under defined conditions remains challenging, including the development of optimal culture conditions for BMSC and large-volume production systems.Conclusions Expansion of BM-MSCs under defined conditions remains challenges, including the development of optimal culture conditions for BMSC and scale-up to large-volume production systems. Optimal values for many culture parameters remain to be identified.

关键词： bone marrow mesenchymal stem cells cell culture cell differentiation in vitro

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Exosomes derived from BMSCs ameliorate cyclophosphamide-induced testosterone deficiency by enhancing the autophagy of Leydig cells via the AMPK-mTOR signaling pathway

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Asian Journal of Andrology 2023年第4期25卷 474-483页

作者： Hao-Yu Liang Fan Peng Min-Jia Pan Sen-Lin Liao Cun Wei Guan-Yang Wei Xiao Xie Kang-Yi Xue Ming-Kun Chen Jian-Kun Yang Wen-Bin Guo Cun-Dong Liu Qi-Zhao Zhou Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China The Third School of Clinical Medicine Southern Medical UniversityGuangzhou 510515China The First School of Clinical Medicine Southern Medical UniversityGuangzhou 510515China

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severelyinfluences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosteronereplacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxictreatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviatecyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders.Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here,we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting theexpression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentrationin serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activatedprotein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos couldbe absorbed by LCs through the blood–testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serumtestosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promoteautophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor,3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exospromote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novelevidence for the clinical improvement of CPTD using BMSCs-exos.

关键词： autophagy bone marrow mesenchymal stem cells cyclophosphamide exosomes Leydig cells testosterone deficiency

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Long non-coding RNA HCAR promotes endochondral bone repair by upregulating VEGF and MMP13 in hypertrophic chondrocyte through sponging miR-15b-5p

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Genes & Diseases 2022年第2期9卷 456-465页

作者： Yun Bai Xiaoshan Gong Rui Dong Zhen Cao Ce Dou Chuan Liu Jianmei Li Fei Kang Jingjin Dai Chunrong Zhao Zhansone Tian Jiulin Tan Qijie Dai Shiwu Dong Department of Biomedical Materials Science School of Biomedical EngineeringThird Military Medical UniversityChongqing 400038PR China Department of Orthopedics Southwest HospitalThird Military Medical UniversityChongqing 400038PR China State Key Laboratory of Trauma Burns and Combined InjuryThird Military Medical UniversityChongqing 400038PR China Institute of Trauma Orthopedics Army General Hospital of PLABeijing 100700PR China

Endochondral bone formation is an important route for bone repair.Although emerging evidence has revealed the functions of long non-coding RNAs(lncRNAs)in bone and cartilage development,the effect of lncRNAs in endochondral bone repair is still largely unknown.Here,we identified a lncRNA,named Hypertrophic Chondrocyte Angiogenesis-related lncRNA(HCAR),and proved it to promote the endochondral bone repair by upregulating the expression of matrix metallopeptidase 13(Mmp13)and vascular endothelial growth factorα(Vegfa)in hypertrophic chondrocytes.Lnc-HCAR knockdown in hypertrophic chondrocytes restrained the cartilage matrix remodeling and decrease the CD31hiEmcnhi vessels number in a bone repair model.Mechanistically,we proved that lnc-HCAR was mainly enriched in the cytoplasm using fluorescence in situ hybridization(FISH)assay,and it acted as a molecular sponge for miR-15b-5p.Further,in hypertrophic chondrocytes,lnc-HCAR competitively bound to miR-15b-5p to increase Vegfa and Mmp13 expression.Our results proved that lncRNA is deeply involved in endochondral bone repair,which will provide a new theoretical basis for future strategies for promoting fracture healing.

关键词： bone marrow mesenchymal stem cells bone repair Chondrocyte Enchondral bone repair Long non coding RNA

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