American Chemical Society
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Bone-Targeting HUVEC-Derived Exosomes Containing miR-503-5p for Osteoporosis Therapy

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Version 2 2023-12-15, 17:36
Version 1 2023-12-12, 17:40
journal contribution
posted on 2023-12-15, 17:36 authored by Haoqiang Huang, Xinting Feng, Ye Feng, Zhen Peng, Chunmeng Jiao, Hui Chen, Chieh Ru Fu, Feng Xu, Yitao Wang, Xiaoping Su, Zhiwen Luo, Qing Wang
Osteoporosis (OP) is a systemic bone disease characterized by decreased bone mass, damaged bone microstructure, increased bone fragility, and increased risk of fractures. It is more common in postmenopausal women and elderly people. The development of drugs with a high bone-targeting ability is urgently needed. We prepared a bioactive nanoparticle that modified the exosomes derived from human umbilical vein endothelial cells (HUVEC-ExomiR‑503‑high) to contain a large amount of miR-503-5p, with a diameter range of 30–150 nm. The HUVEC-ExomiR‑503‑high that we constructed had the same characteristics as ordinary exosomes and could bind to osteoblasts/osteoclasts in vitro. Moreover, they exhibited better bone-targeting ability than exosomes derived from other sources of bone marrow stromal cells in vivo. Bioinformatics analysis showed that miR-503-5p is strongly associated with bone-related pathways. In vitro experiments showed that HUVEC-ExomiR‑503‑high effectively inhibited osteoclast differentiation and promoted osteogenic differentiation. In vivo experiments showed that injecting HUVEC-ExomiR‑503‑high into OP mice significantly increased bone density and prevented OP. HUVEC-ExomiR‑503‑high can be used for bone-targeted therapy of OP, providing an approach to the clinical prevention and treatment of OP.