Extracellular vesicles derived from bone marrow mesenchymal stem cells loaded on magnetic nanoparticles delay the progression of diabetic osteoporosis via delivery of miR-150-5p

作者：Chen Xu, Zhaodong Wang, Yajun Liu, Bangguo Wei, Xiangyu Liu, Keyou Duan, Pinghui Zhou, Zhao Xie, Min Wu, Jianzhong Guan · 发表于：Cell Biology and Toxicology · 年份：2022 · DOI：10.1007/s10565-022-09744-y · 被引用次数：38 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

Abstract Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) are emerged as carriers of therapeutic targets against bone disorders, yet its isolation and purification are limited with recent techniques. Magnetic nanoparticles (MNPs) can load EVs with a unique targeted drug delivery system. We constructed gold-coated magnetic nanoparticles (GMNPs) by decorating the surface of the Fe 3 O 4 @SiO 2 core and a silica shell with poly(ethylene glycol) (PEG)-aldehyde (CHO) and examined the role of BMSC-EVs loaded on GMNPs in diabetic osteoporosis (DO). The osteoporosis-related differentially expressed miR-150-5p was singled out by microarray analysis. DO models were then established in Sprague–Dawley rats by streptozotocin injection, where poor expression of miR-150-5p was validated in the bone tissues. Next, GMNP E was prepared by combining GMNPs with anti-CD63, after which osteoblasts were co-cultured with the GMNP E -BMSC-EVs. The re-expression of miR-150-5p facilitated osteogenesis in osteoblasts. GMNP E could promote the enrichment of EVs in the bone tissues of DO rats. BMSC-EVs delivered miR-150-5p to osteoblasts, where miR-150-5p targeted MMP14 and consequently activated Wnt/β-catenin pathway. This effect contributed to the enhancement of osteoblast proliferation and maturation. Furthermore, GMNP E enhanced the EV-based delivery of miR-150-5p to regulate the MMP14/Wnt/β-catenin axis, resulting in promotion of osteogenesis. Overall, our findings su...