Osteoinduction by bone morphogenetic protein-2 via adenoviral vector under transient immunosuppression.
To examine the effectiveness of gene transfer of bone morphogenetic protein (BMP)-2 in vivo, we evaluated osteoinduction by an adenoviral vector, AxCAOBMP-2, under transient immunosuppression with an immunosuppression drug (cyclophosphamide), which was given at a dose of 125 mg/kg intraperitoneally the day before vector injection. Twenty-five microliters of AxCAOBMP-2 (8.75 x 10(8) pfu, Group I) and AxCALacZ (1.75 x 10(8) pfu, control group) and 5 microliter of AxCAOBMP-2 (1.75 x 10(8) pfu, Group II) were injected into a right calf muscle. On day 21, induced bone in each group was investigated radiologically, histologically, and biochemically. The finding of osteoinduction was only seen in the AxCAOBMP-2-treated groups with immunosuppression. The activity of osteoinduction in Group I was higher than that in Group II. These results suggest that gene therapy with AxCAOBMP-2 under transient immunosuppression may be useful for bone reconstruction.
Okubo
Y
Y
Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. okubo@kuhp@kyoto-u.ac.jp
Bessho
K
K
Fujimura
K
K
Iizuka
T
T
Miyatake
S I
SI
D000256:Adenoviridae; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics*; D003520:Cyclophosphamide / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000000981:diagnostic imaging; D010012:Osteogenesis; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D003520:Cyclophosphamide; D000469:Alkaline Phosphatase; D001616:beta-Galactosidase