Transdifferentiation is the direct conversion from one somatic cell type into another desired somatic cell type.This reprogramming method offers an attractive approach for regenerative medicine.Here,we demonstrate that human umbilical vein endothelial cells(HUVECs)can be transdifferentiated into osteogenic cells via non-viral delivery of minicircle DNA containing Oct4,Sox2,Nanog,and LIN28 polycistronic genes followed by the bone morphogenetic protein-4(BMP-4)treatment.Fluorescence-activated cell sorting analysis revealed transfected cells with minicircle DNA.These transfected cells were then allowed to expand for 6 or 48 hours with or without BMP-4,and we observed a significant endothelial to mesenchymal transition(EMT)transcription markers such as a-SMA via BMP-4 treatment.Furthermore,when the BMP-4 treated cells were exposed to osteogenic medium for additional 2 weeks,alkaline phosphotase showed differentiated cells.These results suggested that the induced osteogenic cells were functional in vitro.Taken together,we successfully demonstrated the direct conversion of HUVEC into osteogenic cells by transduction of reprogramming factors followed by BMP-4.The directed differentiation of endothelial cells into osteogenic cells may have significant utility in vascularized bone tissue engineering applications.