MiR-150-5p-modified Bone Marrow Mesenchymal Stem Cells Derived Exosomes Ameliorate Osteonecrosis of Femoral Head by Promoting Endothelial Cell Angiogenesis

Abstract

Background: Osteonecrosis of femoral head (ONFH) is a common ischemic disease that induces femoral head necrosis. The role of exosomes and miRNA in ONFH has been elucidated, however, whether miRNA-modified exosomes improve the therapy of ONFH is not clear.Methods: We screened ONFH-related miRNAs by RNA sequencing in plasma exosomes of ONFH patients and healthy donors. The key miRNA was overexpressed in bone marrow mesenchymal stem cells (BMSC) exosomes. The regulatory functions of miRNA-modified BMSC exosomes in vascular endothelial cells were illustrated through angiogenesis assay and scratch assay.Results: We identified 9 differently expressed miRNAs (DEmiRNAs) in plasma exosomes between ONFH and healthy groups, with 6 up-regulated and 3 down-regulated miRNAs. Function and pathway analysis revealed DEmiRNAs were primarily involved in angiogenesis, cell migration, focal adhesion. Moreover, miR-150-5p was declined in ONFH exosomes and regulated multiple angiogenesis-related pathways. The miR-150-5p-overexpressed BMSC exosomes were successfully obtained and transported miR-150-5p to endothelial cells. Moreover, the miR-150-5p-modified BMSC exosomes promoted the angiogenesis and migration of endothelial cells.Conclusion: Our results elucidate the exosomal miRNA expression profiles in ONFH, and miR-150-5p-modified BMSC exosomes protect against ONFH by promoting angiogenesis, suggesting a new molecular knowledge for the clinical application of ONFH.

Mechanically activated mesenchymal-derived bone cells drive vessel formation via an extracellular vesicle mediated mechanism

“…For example, miR-150 secreted by monocytes has been shown to induce endothelial tube formation in vitro and angiogenesis in vivo , and down-regulation of miR-150 has been linked to an inhibition of angiogenesis seen in diabetes, cancer, and atherosclerosis. 58 Fang et al 59 elucidated the exosomal miRNA expression profile during osteonecrosis of femoral head (ONFH) and identified that miR-150-5p was significantly downregulated in exosomes within the plasma of the femoral head. Moreover, they demonstrated that miR-150-5p-modified MSC exosomes can promote angiogenesis potentially protecting against ONFH.…”

Mechanically activated bone cells drive vessel formation via an extracellular vesicle mediated mechanism

“…Fang et al elucidated the exosomal miRNA expression profile during osteonecrosis of femoral head (ONFH) and identified that miR-150-5p was significantly downregulated in exosomes within the plasma of the femoral head. Moreover, they demonstrated that miR-150-5p-modified MSC exosomes can promote angiogenesis potentially protecting against ONFH [57]. The target genes of miR-150-5p participate in the TGFβ, MAPK, HIF-1, PI3K-Akt, and mTOR signalling pathways, all of which been linked to angiogenesis.…”