Different osteogenic potentials of recombinant human BMP-6 adeno-associated virus and adenovirus in two rat strains.
The osteogenic potential of AAV5hBMP6 was compared with that of ADhBMP6 in immunodeficient and immunocompetent rats. AAV5hBMP6 (2.3 x 10(12) particles) and ADhBMP6 (5 x 10(7) PFU) elicited viral antibody production in immunocompetent rats. Among rats that received AAV5hBMP6, the earliest time points at which the bone was visible under CT scanner were 30 days in 2-month-old Sprague-Dawley (SD) rats and 60 days in 18-month-old SD rats. The mean volumes of ectopic bone 90 days after viral injection were 0.31 +/- 0.14 cm(3) in athymic nude rats, 0.64 +/- 0.12 cm(3) in 2-month-old SD rats, and 0.21 +/- 0.10 cm(3) in 18-month-old SD rats. In contrast, among rats that received ADhBMP6, the earliest time points to observe the bone formation by CT scan were 15 days in 2-month-old rats and no bone formation in 18-month-old SD rats. The mean volumes of ectopic bone were 4.17 +/- 0.05 cm(3) in athymic nude rats and 0.06 +/- 0.03 cm(3) in 2-month-old SD rats. Although both types of viruses induced an immune response in immunocompetent animals, this response played different roles in the process of bone formation induced by the BMP6 vectors.
Li
Jin Zhong
JZ
Department of Neurological Surgery, University of Virginia Health System, Charlottesville, 22908, USA. jl9v@virginia.edu
Li
Hongwei
H
Hankins
Gerald R
GR
Lieu
Ann-Shung
AS
Noh
El
E
Jacobson
Lindsey
L
Pittman
Debra D
DD
Chiorini
John A
JA
Helm
Gregory A
GA
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013045:Species Specificity; D013997:Time Factors; D014056:Tomography, X-Ray
C525816:BMP6 protein, human; C525818:Bmp6 protein, rat; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins