@article{Sheng2022, 
author = {Chunhui Sheng and Xiaodong Guo and Zhuqing Wan and Xiaoqiang Bai and Hao Liu and Xiao Zhang and Ping Zhang and Yunsong Liu and Wenyue Li and Yongsheng Zhou and Longwei Lv},
title = {Exosomes derived from human adipose-derived stem cells ameliorate osteoporosis through miR-335-3p/Aplnr axis},
year = {2022},
journal = {Nano Research},
volume = {15},
number = {10},
pages = {9135-9148},
keywords = {exosomes, microRNA, osteogenic differentiation, osteoporosis, adipose-derived mesenchymal stem cells},
url = {https://www.sciopen.com/article/10.1007/s12274-022-4554-5},
doi = {10.1007/s12274-022-4554-5},
abstract = {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, miR-335-3p 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.}
}