Bone morphogenetic protein 7-transduced human dermal-derived fibroblast cells differentiate into osteoblasts and form bone in vivo

Abstract

ABSTRACTBackground: Human dermal-derived fibroblast cells (hDDFCs) are multipotent. Bone morphogenetic proteins (BMPs) are a group of cytokines that promote different developmental processes, including the formation of bone. BMPs can promote hDDFC osteogenesis, but the role of BMP7 in hDDFC osteogenesis in vitro and bone formation in vivo has not been investigated in depth. Materials and Methods: hDDFCs were stably transfected with a human BMP7 recombinant adenovirus and osteogenic differentiation was examined by alkaline phosphatase staining and calcium accumulation. In addition, we measured the expression of osteoblast-related genes. To examine osteogenesis in vivo, we injected C57BL/6 nude mice with adenovirus-transfected hDDFCs in a calcium alginate hydrogel and examined bone formation using soft X-ray, histological, and immunohistochemical analyses. Results: Our findings showed that adenovirus-mediated BMP7 expression promoted osteogenic differentiation of hDDFCs and enhanced expression of osteoblast-related genes in vitro. Cells infected with BMP7 adenoviruses showed enhanced bone formation and osteoblast-related gene expression in vivo after the injection of hDDFC–hydrogel mixture. Conclusions: Taken together, our data indicate that BMP7 significantly promotes hDDFC osteogenesis, and confirm that infecting hDDFCs with BMP7-expressing adenoviruses is a useful tool for bone tissue engineering.