Exosomal miR‐423‐5p Derived from Cerebrospinal Fluid Pulsation Stress‐Stimulated Osteoblasts Improves Angiogenesis of Endothelial Cells via DUSP8/ERK1/2 Signaling Pathway

Abstract

Exosomes secreted from osteoblasts (OBs) can regulate the angiogenesis of endothelial cells (ECs); however, whether cerebrospinal fluid pulsation (CSFP) stress, a special mechanical stimulation, can influence the cell’s communication in the context of angiogenesis remains unknown. In this study, the effect of exosomes derived from CSFP stress‐stimulated OBs on facilitating the angiogenesis of ECs was investigated. First, OBs were cultured in a CSFP bioreactor, and exosomes derived from OBs were isolated and identified. Cell Counting Kit 8 assay, transwell migration assay, wound healing migration assay, and tube formation assay were conducted to assess the effects of CSFP stress‐stimulated OBs‐derived exosomes (CSFP‐Exos) on the angiogenesis of ECs. Then high‐throughput RNA sequencing was used to determine the miRNA profiles of Non‐CSFP stress‐stimulated OBs‐derived exosomes (NCSFP‐Exos) and CSFP‐Exos, and the luciferase reporter gene assay was performed to confirm the binging of miR‐423‐5p to DUSP8. In addition, the Matrigel plug assay was performed to explore whether exosomal miR‐423‐5p has the same effects in vivo. Our results suggested that CSFP‐Exos can promote the angiogenesis of ECs, and miR‐423‐5p was enriched in CSFP‐Exos. Moreover, miR‐423‐5p could promote the effect of angiogenesis via directly targeting dual‐specificity phosphatase 8 (DUSP8), which inhibited the ERK1/2 signaling pathway. In conclusion, exosomal miR‐423‐5p derived from CSFP stress‐stimulated OBs could promote the angiogenesis of ECs by the DUSP8/ERK1/2 signaling pathway.