Graphene-Based MicroRNA Transfection Blocks Preosteoclast Fusion to Increase Bone Formation and Vascularization.
Graphene-Based MicroRNA Transfection Blocks Preosteoclast Fusion to Increase Bone Formation and Vascularization.
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DOI：
10.1002/advs.201700578
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Dong S
中科院分区：
文献类型：
--
作者：
Dou C;Ding N;Luo F;Hou T;Cao Z;Bai Y;Liu C;Xu J;Dong S
本研究的目的是设计一种基于石墨烯的 miRNA 转染药物递送系统，用于抗骨吸收治疗。使用负载有 miR-7b 过表达质粒的聚乙烯亚胺（PEI）功能化氧化石墨烯（GO）复合物开发了一种有效的非病毒基因传递系统。 GO-PEI复合物在可接受的细胞毒性范围内表现出优异的转染效率。 GO-PEI-miR-7b 转染后 miR-7b 的过度表达通过阻碍必需的融合分子树突状细胞特异性跨膜蛋白的表达，显着消除破骨细胞（OC）融合和骨吸收活性。然而，破骨细胞生成无需细胞与细胞融合，并且破骨细胞前体（POC）得以保留。通过保存 POC，GO-PEI-miR-7b 转染可促进共培养系统中的间充质干细胞成骨和内皮祖细胞血管生成。在体外和体内，GO-PEI-miR-7b 都会增加 POC 分泌的血小板衍生生长因子-BB。在治疗骨质疏松性卵巢切除小鼠中，GO-PEI-miR-7b 通过增加 CD31hiEmcnhi 细胞数量显着增强骨矿物质密度、骨体积以及骨血管化。这项研究提供了一种细胞-细胞融合靶向 miRNA 转染药物递送策略，用于治疗破骨细胞骨吸收过度的骨疾病。
The objective of this study is to design a graphene‐based miRNA transfection drug delivery system for antiresorptive therapy. An efficient nonviral gene delivery system is developed using polyethylenimine (PEI) functionalized graphene oxide (GO) complex loaded with miR‐7b overexpression plasmid. GO‐PEI complex exhibits excellent transfection efficiency within the acceptable range of cytotoxicity. The overexpression of miR‐7b after GO‐PEI‐miR‐7b transfection significantly abrogates osteoclast (OC) fusion and bone resorption activity by hampering the expression of an essential fusogenic molecule dendritic cell‐specific transmembrane protein. However, osteoclastogenesis occurs without cell–cell fusion and preosteoclast (POC) is preserved. Through preservation of POC, GO‐PEI‐miR‐7b transfection promotes mesenchymal stem cell osteogenesis and endothelial progenitor cells angiogenesis in the coculture system. Platelet‐derived growth factor‐BB secreted by POC is increased by GO‐PEI‐miR‐7b both in vitro and in vivo. In treating osteoporotic ovariectomized mice, GO‐PEI‐miR‐7b significantly enhances bone mineral density, bone volume as well as bone vascularization through increasing CD31hiEmcnhi cell number. This study provides a cell–cell fusion targeted miRNA transfection drug delivery strategy in treating bone disorders with excessive osteoclastic bone resorption.
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DOI：
10.1002/jbmr.2708
发表时间：
2016-01
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Adler RA;El-Hajj Fuleihan G;Bauer DC;Camacho PM;Clarke BL;Clines GA;Compston JE;Drake MT;Edwards BJ;Favus MJ;Greenspan SL;McKinney R Jr;Pignolo RJ;Sellmeyer DE
通讯作者：
Sellmeyer DE
影响因子：
9.5
作者：
Ding, Zhijia;Zhang, Zhijun;Chen, Yanyan
通讯作者：
Chen, Yanyan
影响因子：
15
作者：
Tang, Lena Ai Ling;Wang, Junzhong;Loh, Kian Ping
通讯作者：
Loh, Kian Ping
影响因子：
8.6
作者：
Hong, X;Li, J;Li, TJ
通讯作者：
Li, TJ
DOI：
10.1073/pnas.031577698
发表时间：
2001-01-30
影响因子：
11.1
作者：
Putnam, D;Gentry, CA;Langer, R
通讯作者：
Langer, R