|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Lysine-specific demethylase 1 inhibitor rescues the osteogenic ability of mesenchymal stem cells under osteoporotic conditions by modulating H3K4 methylation显示文摘Bone tissue engineering may be hindered by underlying osteoporosis because of a decreased osteogenic ability of autologous seed cells and an unfavorably changed microenvironment in these patients. Epigenetic regulation plays an important role in the developmental origins of osteoporosis; however, few studies have investigated the potential of epigenetic therapy to improve or rescue the osteogenic ability of bone marrow mesenchymal stem cells(BMMSCs) under osteoporotic conditions. Here, we investigated pargyline, an inhibitor of lysine-specific demethylase 1(LSD1), which mainly catalyzes the demethylation of the di- and mono-methylation of H3K4. We demonstrated that 1.5 mmol·L^(- 1)pargyline was the optimal concentration for the osteogenic differentiation of human BMMSCs. Pargyline rescued the osteogenic differentiation ability of mouse BMMSCs under osteoporotic conditions by enhancing the dimethylation level of H3K4 at the promoter regions of osteogenesis-related genes. Moreover, pargyline partially rescued or prevented the osteoporotic conditions in aged or ovariectomized mouse models, respectively. By introducing the concept of epigenetic therapy into the field of osteoporosis, this study demonstrated that LSD1 inhibitors could improve the clinical practice of MSC-based bone tissue engineering and proposes their novel use to treat osteoporosis. | Longwei Lv Wenshu Ge Yunsong Liu Guanyou Lai Hao Liu Wenyue Li Yongsheng Zhou | 2016 | Bone Research2016，4，4： | 11 |
| 2 | Exosomes derived from human adipose-derived stem cells ameliorate osteoporosis through miR-335-3p/Aplnr axis显示文摘Treatment of osteoporosis is still a challenge in clinic,which leads to an increasing social burden as the aging of population.Exosomes originated from human adipose-derived stem cells(hASCs)hold promise to promote osteogenic differentiation,thus may ameliorate osteoporosis.The main purpose of this study was to investigate the novel usage of hASC-derived exosomes in the treatment of osteoporosis and their underlying mechanism.Two types of exosomes,i.e.,exosomes derived from hASCs cultured in proliferation medium(P-Exos)and osteogenic induction medium(O-Exos),were obtained.As compared with P-Exos,O-Exos could promote the osteogenic differentiation of mouse bone marrow-derived stem cells(mBMSCs)from osteoporotic mice in vitro and ameliorated osteoporosis in vivo.Then,microRNA(miRNA)-335-3p was identified to be the key differentially expressed microRNA between the two exosomes by small RNA sequencing,gene overexpression and knock-down,qRT-PCR,and dual-luciferase reporter assay,and Aplnr was confirmed to be the potential target gene of miRNA-335-3p.In addition,miR335-3p inhibitor-optimized O-Exos were established by transfection of miR-335-3p inhibitor,which significantly enhanced the osteogenic differentiation of mBMSCs in vitro,and bone density and number of trabecular bones in vivo compared with unoptimized O-Exos.Our results indicated that the ASC-exosome-based therapy brings new possibilities for osteoporosis treatment.Besides,engineered exosomes based on transfection of miRNA are a promising strategy to optimize the therapeutic effect of exosomes on osteoporosis. | Chunhui Sheng Xiaodong Guo Zhuqing Wan Xiaoqiang Bai Hao Liu Xiao Zhang Ping Zhang Yunsong Liu Wenyue Li Yongsheng Zhou Longwei Lv | 2022 | Nano Research2022，15，10： | 1 |
| 3 | The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis显示文摘Understanding mechanisms underlying the heterogeneity of multipotent stem cells offers invaluable insights into biogenesis and tissue development. Extracellular matrix (ECM) stiffness has been acknowledged as a crucial factor regulating stem cell fate. However, how cells sense stiffness cues and adapt their metabolism activity is still unknown. Here we report the novel role of mitochondrial phosphoenolpyruvate carboxykinase (PCK2) in enhancing osteogenesis in 3D ECM via glycolysis. We experimentally mimicked the physical characteristics of 3D trabeculae network of normal and osteoporotic bone with different microstructure and stiffness, observing that PCK2 promotes osteogenesis in 3D ECM with tunable stiffness in vitro and in vivo. Mechanistically, PCK2 enhances the rate-limiting metabolic enzyme pallet isoform phosphofructokinase (PFKP) in 3D ECM, and further activates AKT/extracellular signal-regulated kinase 1/2 (ERK1/2) cascades, which directly regulates osteogenic differentiation of MSCs. Collectively, our findings implicate an intricate crosstalk between cell mechanics and metabolism, and provide new perspectives for strategies of osteoporosis. | Zheng Li Muxin Yue Xuenan Liu Yunsong Liu Longwei Lv Ping Zhang Yongsheng Zhou | 2022 | Bioactive Materials2022，7，12： | 1 |
| 4 | Characterization of mesenchymal stem cells in human fetal bone marrow by single-cell transcriptomic and functional analysis显示文摘Bone marrow mesenchymal stromal/stem cells (MSCs) are a heterogeneous population that can self-renew and generate stroma,cartilage, fat, and bone. Although a significant progress has been made toward recognizing about the phenotypic characteristics ofMSCs, the true identity and properties of MSCs in bone marrow remain unclear. Here, we report the expression landscape of humanfetal BM nucleated cells (BMNCs) based on the single-cell transcriptomic analysis. Unexpectedly, while the common cell surfacemarkers such as CD146, CD271, and PDGFRa used for isolating MSCs were not detected, LIFR+PDGFRB+ were identified to bespecific markers of MSCs as the early progenitors. In vivo transplantation demonstrated that LIFR+PDGFRB+CD45-CD31-CD235a-MSCs could form bone tissues and reconstitute the hematopoietic microenvironment (HME) effectively in vivo. Interestingly, wealso identified a subpopulation of bone unipotent progenitor expressing TM4SF1+CD44+CD73+CD45-CD31-CD235a-, which hadosteogenic potentials, but could not reconstitute HME. MSCs expressed a set of different transcription factors at the different stagesof human fetal bone marrow, indicating that the stemness properties of MSCs might change during development. Moreover,transcriptional characteristics of cultured MSCs were significantly changed compared with freshly isolated primary MSCs. Ourcellular profiling provides a general landscape of heterogeneity, development, hierarchy, microenvironment of the human fetal BMderivedstem cells at single-cell resolution. | Ping Zhang Ji Dong Xiaoying Fan Jun Yong Ming Yang Yunsong Liu Xiao Zhang Longwei Lv Lu Wen Jie Qiao Fuchou Tang Yongsheng Zhou | 2023 | Signal Transduction and Targeted Therapy2023，8，4： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员