Growth and differentiation factor-5 (GDF-5) stimulates osteogenic differentiation and increases vascular endothelial growth factor (VEGF) levels in fat-derived stromal cells in vitro

Fat-derived adult mesenchymal stem cells can differentiate into different phenotypes reflecting their potential to regenerate various skeletal tissues. These properties together with the association of adipose with skeletal tissues formed the basis of our study to establish an experimental model for using fat-derived stromal cells to undergo osteogenic differentiation in vitro under the influence of either growth and differentiation factor-5 (GDF-5) or bone morphogenetic protein-2 (BMP-2). Members of the BMP/GDF family of proteins are known for their ability to elicit skeletal morphogenesis, but little is known about the mechanism whereby these morphogens exert their effect on the osteogenic differentiation of fat-derived stromal cells. We compared the effects of GDF-5 and BMP-2 in their recombinant forms to qualitatively and quantitatively determine their influence on the osteogenic differentiation of fat derived stromal cells by examining the effects on mineralization, extracellular matrix, cell proliferation, biochemistry, and gene expression. We identified that GDF-5 not only promotes osteogenic differentiation of rat fat-derived stromal cells, but also may promote angiogenic activity of stromal cells by increasing vascular endothelial growth factor (VEGF) gene expression in vitro. These data suggest that several distinct regulatory mechanisms may exist in association with osteogenic differentiation.