MicroRNA-126 promotes proliferation, migration, invasion and endothelial differentiation while inhibits apoptosis and osteogenic differentiation of bone marrow-derived mesenchymal stem cells

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used for the treatment of inflammatory and immune diseases, and microRNA-126 (miR-126) is a critical regulator in inflammation as well as immunity. However, the mediating role of miR-126 in BMSCs is still not clear. Thus, this study aimed to preliminarily investigate the effect of miR-126 on proliferation, apoptosis, migration, invasion, differentiation, and its potential regulating pathways in BMSCs. Human BMSCs were obtained and infected with miR-126 overexpression lentivirus, control overexpression lentivirus, miR-126 knock-down lentivirus and control knock-down lentivirus, then cell functions, the PI3 K/AKT pathway and MEK1/ERK1 pathway were evaluated. Subsequently, PI3 K overexpression plasmid and MEK1 overexpression plasmid were transfected into BMSCs with miR-126 knockdown, then the cell functions were assessed as well. BMSCs with miR-126 overexpression displayed elevated proliferation, migration and invasion while decreased apoptosis; however, BMSCs with miR-126 knockdown presented with decreased proliferation, migration, invasion but increased apoptosis. As for differentiation, BMSCs with miR-126 overexpression showed higher levels of CD31, eNOS and VE-cadherin but lower expressions of ALP, OPN and RUNX2, while BMSCs with miR-126 knockdown disclosed the opposite results. Additionally, BMSCs with miR-126 overexpression showed elevated PI3 K, pAKT, MEK1 and pERK1 expressions, while BMSCs with miR-126 knockdown displayed opposite results. Furthermore, PI3 K overexpression and MEK1 overexpression both reversed the effects of miR-126 on cell functions in BMSCs. In conclusion, miR-126 is a genetic regulator in BMSCs via modulating multiple cell functions through the PI3 K/AKT and MEK1/ERK1 signaling pathways.