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.
Cell Biol Toxicol
; 39(4): 1257-1274, 2023 08.
Article
em En
| MEDLINE
| ID: mdl-36112264
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 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/ß-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/ß-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. 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/ß-catenin and increases osteogenesis. 4. miR-150-5p activates the Wnt/ß-catenin pathway by downregulating MMP14.
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Base de dados:
MEDLINE
Assunto principal:
Osteoporose
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MicroRNAs
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Diabetes Mellitus
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Nanopartículas de Magnetita
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Células-Tronco Mesenquimais
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Vesículas Extracelulares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article