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, AxCAOBMP-2, in normal rats (Group I) and 2 immunosuppressed groups (Groups II and III). Immunosuppression was induced by 125 mg/kg of cyclophosphamide injected intraperitoneally the day before vector injection. Groups I and III received a high dose of AxCAOBMP-2 (25 microl; 8.75 x 10(8) pfu) and Group II a low dose (5 microl; 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, histologically, immunohistochemically and biochemically. Osteoinduction was observed only in Groups II and III on days 14 and 21. The activity of osteoinduction in Group III was higher than that in Group II. There was little difference 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 was that most of the infected cells were eliminated by the immune system of the host from days 3 to 7. These results suggest that gene therapy with AxCAOBMP-2 under transient immunosuppression may be useful for bone reconstruction.
Okubo
Y
Y
Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Japan.
Bessho
K
K
Fujimura
K
K
Kaihara
S
S
Iizuka
T
T
Miyatake
S
S
D000256:Adenoviridae / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002118:Calcium / Q000032:analysis; D003520:Cyclophosphamide / Q000494:pharmacology; D015316:Genetic Therapy; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008297:Male; D010012:Osteogenesis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D003520:Cyclophosphamide; D000469:Alkaline Phosphatase; D002118:Calcium