Vitamin K2 promotes mesenchymal stem cell differentiation by inhibiting miR-133a expression

Abstract

Vitamin K2 has been demonstrated to promote the osteogenic differentiation of mesenchymal stem cells; however, the mechanisms underlying this effect remain unclear. As microRNA (miR)-133a has been identifed as a negative regulator of osteogenic differentiation, the present study hypothesized that vitamin K2 promoted osteogenesis by inhibiting miR-133a. Using human bone marrow stromal cells (hBMSCs) overexpressing miR-133a, or a control, the expression levels of osteogenesis-associated proteins, including runt-related transcription factor 2, alkaline phosphatase and osteocalcin, were analyzed. miR-133a signifcantly suppressed the osteogenic differentiation of hBMSCs. To determine the effect of vitamin K2 on miR-133a expression and osteogenesis, hBMSCs were treated with vitamin K2. Vitamin K2 inhibited miR-133a expression, which was accompanied by enhanced osteogenic differentiation. Furthermore, the expression levels of vitamin K epoxide reductase complex subunit 1, the key protein in γ-carboxylation, were downregulated by miR-133a overexpression and upregulated by vitamin K2 treatment, indicating a positive feedback on γ-carboxylation. The results of the present study suggested that vitamin K2 targets miR-133a to regulate osteogenesis.