Bone morphogenetic protein 7 enhances the osteogenic differentiation of human dermal-derived CD105+ fibroblast cells through the Smad and MAPK pathways

Abstract

The skin, as the largest organ of the human body, is an important source of stromal stem cells with multipotent differentiation potential. CD 105+ mesenchymal stem cells exhibit a higher level of stemness than CD 105- cells. In the present study, human dermal-derived CD 105+ fibroblast cells (CD 105+ hDD FCs) were isolated from human foreskin specimens using immunomagnetic isolation methods to examine the role of bone morphogenetic protein (BMP)-7 in osteogenic differentiation. Adenovirus-mediated recombinant BMP7 expression enhanced osteogenesis-associated gene expression, calcium deposition, and alkaline phosphatase activity. Investigation of the underlying mechanisms showed that BMP7 activated small mothers against decapentaplegic (Smad) and p38/mitogen-activated protein kinase signaling in CD 105+ hDD FCs. The small interfering RNA-mediated knockdown of Smad4 or inhibition of p38 attenuated the BMP7-induced enhancement of osteogenic differentiation. In an in vivo ectopic bone formation model, the adenovirus-mediated overexpression of BMP7 enhanced bone formation from CD 105+ hDD FCs. Taken together, these data indicated that adenoviral BMP7 gene transfer in CD 105+ hDD FCs may be developed as an effective tool for bone tissue engineering.