Journal Article

Graphene‐Based MicroRNA Transfection Blocks Preosteoclast Fusion to Increase Bone Formation and Vascularization

Hou, Tianyong, Dong, Shiwu, Ding, Ning, Dou, Ce, Bai, Yun, Liu, Chuan, Luo, Fei, Xu, Jianzhong, Cao, Zhen

2018

Overview

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. A graphene based miRNA transfection system is developed using graphene oxide (GO)‐PEI loaded with miR‐7b plasmid. GO‐PEI‐miR‐7b efficiently delivers miR‐7b plasmid into bone marrow macrophages and reduces the expression of target protein dendritic cell‐specific transmembrane protein (DC‐STAMP) thus blocking cell‐cell fusion to preserve pre‐osteoclasts for better osteogenesis and angiogenesis.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Angiogenesis / Apoptosis / Cytotoxicity / dendritic cell‐specific transmembrane protein (DC‐STAMP) / Deoxyribonucleic acid / DNA / Graphene / graphene oxide / MicroRNAs / miRNA / osteoclasts / Osteoporosis / Proteins / vascularization / Vectors (Biology)