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Exosomal MMP2 derived from mature osteoblasts promotes angiogenesis of endothelial cells via VEGF/Erk1/2 signaling pathway
- Source :
- Experimental cell research. 383(2)
- Publication Year :
- 2019
-
Abstract
- The skeletal system is a dynamic organ that continuously undergoes coupled trabeculae and blood vessels remodeling, indicating the possible existence of molecular crosstalk between endothelial and osteoblastic cells. Since the cross-talk between bone-forming osteoblasts (OBs) and vessel-forming endothelial cells (ECs) have progressively gained investigators' attention, few studies focused on the regulatory function of extracellular vesicles derived from OBs on ECs. In this study, the effect of the exosomes derived from mature osteoblasts (MOBs) on the ECs was investigated. Firstly, exosomes derived from mature osteoblasts (MOB-Exos) were isolated and identified by NanoSight light scatter technology, electron microscopy and Western bolting. Fluorescent labeling of MOB-Exos revealed its internalization by ECs. RNA interference technique was used to knock down matrix metalloproteinase-2 (MMP2) in MOB-Exos. Then ECs were co-cultured with MOB-Exos and MMP2 knockdown MOB-Exos. Wound healing migration assay, transwell migration assay, CCK-8 assay and tube formation assay of ECs were conducted to determine the angiogenic capability of ECs. Then the VEGF/Erk1/2 pathway markers were detected by Western blot. Our results showed that MOB-Exos could promote the proliferation, migration and tube formation of ECs. Meanwhile, the promoted angiogenetic capacities of ECs were impaired when MMP2 in MOB-Exos was knocked down. In addition, immunoblotting indicated that MOB-Exos could promote the activation of the VEGF/Erk1/2 pathway of ECs; whereas the activation of the VEGF/Erk1/2 pathway was attenuated when the ECs were co-cultured with the MMP2 knockdown MOB-Exos. In conclusion, the MMP-2 existing in exosomes derived from MOBs could promote the angiogenesis of ECs in vitro, which might be realized through VEGF/Erk1/2 signaling pathway.
- Subjects :
- 0301 basic medicine
Vascular Endothelial Growth Factor A
MMP2
Angiogenesis
MAP Kinase Signaling System
Neovascularization, Physiologic
Biology
Exosomes
03 medical and health sciences
Mice
0302 clinical medicine
Animals
Cells, Cultured
Tube formation
Gene knockdown
Wound Healing
Migration Assay
Osteoblasts
Endothelial Cells
Cell Differentiation
Cell Biology
Microvesicles
Coculture Techniques
Cell biology
030104 developmental biology
030220 oncology & carcinogenesis
Matrix Metalloproteinase 2
Signal transduction
Wound healing
Signal Transduction
Subjects
Details
- ISSN :
- 10902422
- Volume :
- 383
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....8de9f4642a519e796555190f768a0341