锶离子外泌体促间充质干细胞成骨分化和内皮细胞血管生成的实验研究

Abstract

Abstract: Objective:To explore the effect of mesenchymal stem cell (MSC) derived exosomes induced by strontium on osteogenic differentiation and angiogenesis, providing a new idea for the repair of vascularized bone defects. Methods:Strontium was added to bone marrow mesenchymal stem cell (BMSC) and strontium-exosomes were then extracted by ultracentrifugation, using untreated BMSC exosomes as control. The cell internalization was observed by fluorescent labeling of exosomes. Alkaline phosphatase (ALP) staining, ALP activity determination and qRT-PCR analysis were used to study the effects of exosomes on the osteogenic differentiation of BMSC. The effects of exosomes on vascular formation of endothelial cells in vitro were evaluated by wound healing assay, transwell assay, tube formation assay and other methods. Finally, the potential mechanism of strontium-exosomes in promoting osteogenesis and angiogenesis was discussed by the miRNA sequencing. Results:The stimulation of strontium ion could not affect the secretion of exosomes by BMSC, and the strontium-exosomes could be internalized by BMSC. Strontium-exosomes could enhance the ALP activity of BMSC and up-regulate the transcription of osteogenesis-related genes ALP and runt-related transcription factor 2 (Runx2). Strontium-exosomes could also promote the migration and the tubule formation of endothelial cells, and significantly increase the transcription of angiogenic-related genes of VEGF, ANG1 and FGF. The miRNA sequencing analysis revealed that the stimulation of strontium ions induced the differential expression of miRNA in exosomes derived from BMSC. The up-regulated expression of miR-125b-5p, miR-132-3p, miR-31a-5p and miR-450b may be then involved in promoting osteogenic differentiation and angiogenesis of cells. Conclusions:The strontium-exosomes have dual functions of promoting angiogenesis and osteogenic differentiation.

Key words: bone tissue engineering, strontium ion, exosome, osteogenic differentiation, angiogenesis

References 20

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The study of strontium-induced MSC-derived exosomes in promoting osteogenic differentiation of mesenchymal stem cells and angiogenesis of endothelial cells

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