Delivery of miR-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting GFAP.
Cell Biol Toxicol
; 40(1): 52, 2024 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-38967699
ABSTRACT
Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNPE-EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNPE targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNPE-EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNPE-EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Osteoclastos
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Osteoporosis
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Ratas Sprague-Dawley
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MicroARNs
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Células Madre Mesenquimatosas
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Vesículas Extracelulares
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Proteína Ácida Fibrilar de la Glía
Límite:
Animals
Idioma:
En
Revista:
Cell Biol Toxicol
/
Cell biol. toxicol
/
Cell biology and toxicology
Asunto de la revista:
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China