Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head

Abstract

Traumatic osteonecrosis of the femoral head (ONFH) is a condition leading to the collapse of the femoral head, and the primary treatment is a total hip replacement, which has a poor prognosis. The current study was conducted with the aim of investigating the role of exosomes from bone marrow-derived mesenchymal stem cells (BM-MSCs) carrying microRNA-224-3p (miR-224-3p) in traumatic ONFH. Initially, a microarray analysis was performed to screen the differentially expressed genes and miRs associated with traumatic ONFH. Patients with traumatic and nontraumatic ONFH were enrolled, and HUVECs were obtained. The BM-MSCs-derived exosomes were purified and characterized, after which HUVECs were cocultured with exosomes. The functional role of miR-224-3p in traumatic ONFH was determined using ectopic expression, depletion, and reporter assay experiments. Endothelial cell proliferation, migration, invasion abilities, and angiogenesis were evaluated. Based on microarray analysis, miR-224-3p was found to be down-regulated, whereas focal adhesion kinase family interacting protein of 200 kDa (FIP200) was up-regulated in ONFH. Traumatic ONFH exosomes resulted in the up-regulation of FIP200 and down-regulation of miR-224-3p. FIP200 was confirmed to be a target gene of miR-224-3p. Exosomes were internalized by vascular endothelial cells. The down-regulation of exosomal miR-224-3p was observed to promote endothelial cell proliferation, migration, invasion abilities, angiogenesis, and FIP200 expression. In addition, FIP200 overexpression promoted angiogenesis. In summary, the results highly indicated that lower miR-224-3p levels in exosomes derived from BM-MSCs promote angiogenesis of traumatic ONFH by up-regulating FIP200. The present study provides a potential strategy for the treatment of traumatic ONFH.-Xu, H.-J., Liao, W., Liu, X.-Z., Hu, J., Zou, W.-Z., Ning, Y., Yang, Y., Li, Z.-H. Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head.

Keywords: FIP200; endothelial cells; exosomes; proliferation; targeting regulation.