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

Abstract

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 PPARγ-2 and the total droplet number after adipogenic induction. In addition, Foxc2 enhanced the expression of β-catenin, an important modulator of osteoblastogenesis. XAV939, a small molecule inhibitor of the Wnt-β-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-β-catenin signaling pathway.

Comparative Investigation of Human Amniotic Epithelial Cells and Mesenchymal Stem Cells for Application in Bone Tissue Engineering

“…In fact, several studies have described the essential roles of FOXC2 in skeletal development and osteogenesis, including the capability to enhance osteogenic differentiation in various cells and indispensable roles in neurocranium and vertebrae development [ 42 – 45 ]. Interestingly, FOXC2 has also been reported to inhibit adipogenic differentiation and was associated with bone mineral density in community-dwelling Japanese individuals [ 46 – 48 ]. As the reciprocal relationship between osteogenesis and adipogenesis during mesodermal differentiation has been most clearly elucidated, our observation together with previous studies indicates a potential key role of FOXC2 in early osteoblastic phenotype commitment and bone metabolism.…”

Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide‐induced apoptosis partially by inhibiting the Wnt/β‐catenin pathway

“…Adult stem cells are tissue-specific cells that retain the ability to differentiate into a variety of cell lineages and have self-renewal capabilities (Xia and Cao, 2013;You et al, 2013). Mesenchymal stem cells (MSCs) are one class of adult stem cells that have generated a significant amount of interest as a potential therapy for lung disease (Mei et al, 2007;Mei et al, 2010;Lee et al, 2011;Barisione et al, 2014).…”

α-MSH and Foxc2 promote fatty acid oxidation through C/EBPβ negative transcription in mice adipose tissue

“…Our previous studies found Foxc2 enhanced mice pre-adipocytes proliferation and inhibited apoptosis via activating Akt/mTORC1 signaling pathway23. Foxc2 stimulates osteogenic differentiation and inhibits adipogenic differentiation in bone marrow mesenchymal stem cells, and in white adipocytes2425. Overexpression of Foxc2 in adipocytes prevents diet-induced obesity and insulin resistance2627.…”