Abstract
AbstractExtracellular 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 Fe3O4@SiO2 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, GMNPE was prepared by combining GMNPs with anti-CD63, after which osteoblasts were co-cultured with the GMNPE-BMSC-EVs. The re-expression of miR-150-5p facilitated osteogenesis in osteoblasts. GMNPE 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, GMNPE 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 suggest the potential of GMNP-BMSC-EVs to strengthen osteoblast proliferation and maturation in DO, showing promise as an appealing drug delivery strategy against DO.
Graphical abstract
1. GMNPs-BMSCs-EVs-miR-150-5p promotes the osteogenesis of DO rats.
2. miR-150-5p induces osteoblast proliferation and maturation by targeting MMP14.
3. Inhibition of MMP14 activates Wnt/β-catenin and increases osteogenesis.
4. miR-150-5p activates the Wnt/β-catenin pathway by downregulating MMP14.
Funder
Key Project of Natural Science of Bengbu Medical College
Key Project of Natural Science Research of Anhui Province
Publisher
Springer Science and Business Media LLC
Subject
Health, Toxicology and Mutagenesis,Cell Biology,Toxicology
Cited by
8 articles.
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