Osteoinduction by bone morphogenetic protein 2-expressing adenoviral vector: application of biomaterial to mask the host immune response.
We constructed a human bone morphogenetic protein 2 (BMP-2)-expressing adenoviral vector, AxCABMP-2, which showed osteoinduction in immunosuppressed rats. In immunocompetent rats, new bone was not induced, because of the rapid elimination of transduced cells. Biomaterials such as collagen can be used as carriers for the delivery of DNA vectors, allowing prolonged expression of plasmid DNA in normal animals. We evaluated osteoinduction with AxCABMP-2 and atelopeptide type I collagen in immunocompetent rats. Collagen plus AxCABMP-2 (BMP group), collagen plus AxCALacZ (LacZ group), or collagen alone (CL group) was implanted into calf muscle pouches in immunocompetent rats, or AxCABMP-2 alone (injection group) was injected into the calf muscle. On days 3, 7, 14, and 21 after treatment, osteoinduction was evaluated. In the BMP group, bone formation was not observed on days 3 and 7. On day 14, radiographic formation was seen, but little bone formation was detected histologically. On day 21, new bone formation was observed both radiologically and histologically. In the other groups, osteoinduction was not found at any time. Immunohistochemical analysis on days 3 and 7 revealed decreased immunogenicity in the BMP group compared with the injection group. These findings suggested that collagen was an effective masking material for our vector.
Sonobe
Junya
J
Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Okubo
Yasunori
Y
Kaihara
Shinji
S
Miyatake
Shin-Ichi
S
Bessho
Kazuhisa
K
D000256:Adenoviridae / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle; D003094:Collagen / Q000737:chemistry* / Q000494:pharmacology; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007121:Immunocompetence; D008297:Male; D009132:Muscles / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; C059821:atelocollagen; D003094:Collagen; D000469:Alkaline Phosphatase