Foxc2 over-expression in bone marrow mesenchymal stem cells stimulates osteogenic differentiation and inhibits adipogenic differentiation

The forkhead box C2 (Foxc2) protein, a member of the forkhead/winged helix transcription factor family, is strongly expressed in developing embryo and is required in various developmental processes. However, the precise function of Foxc2 in osteoblast differentiation remains largely unknown. The present study investigated the role of Foxc2 overexpression on osteogenic and adipogenic differentiations. In our experiment, rabbit bone marrow mesenchymal stem cells (BMSCs) were transduced with lentiviral vectors containing Foxc2 or green fluorescent protein (GFP), and the gene expression and biological activity of Foxc2 were examined in vitro. The results showed that the mRNA and protein expressions of Foxc2 were stable and high in cells transduced with Foxc2 compared with those transduced with GFP. The overexpression of Foxc2 increased the mRNA and protein levels of COLI, OCN, and OPN; enhanced the activity of ALP after osteogenic induction; and decreased the expression of PPAR gamma-2 and the total droplet number after adipogenic induction. In addition, Foxc2 enhanced the expression of beta-catenin, an important modulator of osteoblastogenesis. XAV939, a small molecule inhibitor of the Wnt-beta-catenin pathway, suppressed Foxc2-mediated regulation of BMSC differentiation. These findings demonstrate that the overexpression of Foxc2 gene in BMSCs may promote osteogenic differentiation and inhibit adipogenic differentiation, and this effect can be mediated via activating the canonical Wnt-beta-catenin signaling pathway.