Osteoinduction by bone morphogenetic protein-2 via adenoviral vector undertransient immunosuppression

To examine the effectiveness of gene transfer of bone morphogenetic protein (BMP)-2 in vivo, we evaluated osteoinduction by an adenoviral vector, AxCA OBMP-2, under transient immunosuppression with an immunosuppression drug (c yclophosphamide), which was given at a dose of 125 mg/kg intraperitoneally the day before vector injection. Twenty-five microliters of AxCAOBMP-2 (8.7 5 x 10(8) pfu, Group I) and AxCALacZ (1.75 x 10(8) pfu, control group) and 5 mu l of AxCAOBMP-2 (1.75 x 108 pfu, Group II) were injected into a right calf muscle. On day 21, induced bone in each group was investigated radiolo gically, histologically, and biochemically, The finding of osteoinduction w as only seen in the AxCAOBMP-2 treated groups with immunosuppression, The a ctivity of osteoinduction in Group I was higher than that in Group II. Thes e results suggest that gene therapy with AxCAOBMP-2 under transient immunos uppression may be useful for bone reconstruction. (C) 2000 Academic Press.