MiR-214 suppresses the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and These effects are mediated through the inhibition of the JNK and p38 pathways

Abstract

In this study, we sought to investigate the expression of microRNA (miR)-214 on the osteogenic differentiation of bone marrow.derived mesenchymal stem cells (BMSCs) and explore the possible underlying mechanisms. We found that the overexpression of miR.214 effectively promoted the adipocyte differentiation of BMSCs in vitro, reduced alkaline phosphatase (ALP) activity and the gene expression of collagen type I (Col I), osteocalcin (OCN) and osteopontin (OPN) in the BMSCs. We further found that the overexpression of miR.214 suppressed the protein expression of fibroblast growth factor (FGF), phosphorylated c.Jun N-terminal kinase (p-JNK) and phosphorylated p38 (p-p38) in the BMSCs. The downregulation of miR.214 promoted the osteogenic differentiation of BMSCs, and increased ALP activity and Col I, OCN and OPN gene expression in the BMSCs. It also increased FGF p-JNK and p-p38 protein expression in the BMSCs. The use of JNK inhibitor (SP600125) enhanced the inhibitory effects of miR.214 overexpression on osteogenic differentiation, ALP activity, and Col I, OCN and OPN gene expression in the BMSCs. Lastly, the use of p38 inhibitor (SB202190) also enhanced the inhibitory effects of miR.214 overexpression on ALP activity, and Col I, OCN and OPN gene expression in the BMSCs. These results provide a mechanism responsible for the suppressive effects of miR.214 on the osteogenic differentiation of BMSCs involving the inhibition of the JNK and p38 pathways.