The time course study of osteoinduction by bone morphogenetic protein-2 via adenoviral vector

We evaluated the time course of osteoinduction by an adenoviral vector, AxC AOBMP-2, in normal rats (Group I) and 2 immunosuppressed groups (Groups II and III). Immunosuppression was induced by 125 mg/kg of cyclophosphamide in jected intraperitoneally the day before vector injection. Groups I and III received a high dose of AxCAOBMP-2 (25 mul; 8.75 x 10(8) pfu) and Group II a low dose (5 mul; 1.75 x 10(8) pfu). Each dose of AxCAOBMP-2 was injected into the right calf muscle of rats. On days 7, 14 and 21 postinjection, the osteoinducive activity in each group was investigated radiologically, hist ologically, immunohistochemically and biochemically. Osteoinduction was obs erved only in Groups II and III on days 14 and 21. The activity of osteoind uction in Group III was higher than that in Group II. There was little diff erence in the expression of LacZ between Groups I and III on day 3. However , there was a marked difference in BMP-2 protein expression between Groups I and III on day 7 postinjection. We speculated that the reason for this wa s that most of the infected cells were eliminated by the immune system of t he host from days 3 to 7. These results suggest that gene therapy with AxCA OBMP-2 under transient immunosuppression may be useful for bone reconstruct ion. (C) 2001 Elsevier Science Inc. All rights reserved.