Bioinspired Nanovesicles Convert the Skeletal Endothelium-Associated Secretory Phenotype to Treat Osteoporosis
Yongzhi Cui, Zhongying Li, Yuanyuan Guo, Xiangbei Qi, Yuehua Yang, Xiong Jia, Rui Li, Jingyu Shi, Weihang Gao, Zhengwei Ren, Guohui Liu, Qingsong Ye, Zhiping Zhang, Dehao Fu
Journal：ACS Nano
IF：18.03
DOI：10.1021/acsnano.2c03781
PMID：35801837
Published：2022-07-08
research field：肿瘤学消化生物学呼吸生物学
Abstract
Recently, bone marrow endothelial cells (BMECs) were found to play an important role in regulating bone homeostasis. However, few studies utilized BMECs to treat bone metabolic diseases including osteoporosis. Here, we reported bioinspired nanovesicles (BNVs) prepared from human induced pluripotent stem cells-derived endothelial cells under hypoxia culture through an extrusion approach. Abundant membrane C-X-C motif chemokine receptor 4 conferred these BNVs bone-targeting ability and the endothelial homology facilitated the BMEC tropism. Due to their unique endogenous miRNA cargos, these BNVs re-educated BMECs to secret cytokines favoring osteogenesis and anti-inflammation. Owing to the conversion of secretory phenotype, the osteogenic differentiation of bone mesenchymal stem cells was facilitated, and the M1-macrophage-dominant pro-inflammatory microenvironment was ameliorated in osteoporotic bones. Taken together, this study proposed BMEC-targeting nanovesicles treating osteoporosis via converting the skeletal endothelium-associated secretory phenotype.
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