Osteogenic gene regulation and relative acceleration of healing by adenoviral-mediated transfer of human BMP-2 or -6 in equine osteotomy and ostectomy models

Authors

  • Akikazu Ishihara,

    1. Comparative Orthopedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, 601 Tharp Street, Columbus, Ohio 43210
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  • Kathleen M. Shields,

    1. Women's Health and Bone/Wyeth Research, Cambridge, Massachusetts
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  • Alan S. Litsky,

    1. Orthopaedic BioMaterials Laboratory, Departments of Orthopaedics and Biomedical Engineering, The Ohio State University, Columbus, Ohio
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  • John S. Mattoon,

    1. Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington
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  • Steven E. Weisbrode,

    1. Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio
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  • Jeffrey S. Bartlett,

    1. Gene Therapy Center, Columbus Children's Research Institute, Columbus Children's Hospital, Columbus, Ohio
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  • Alicia L. Bertone

    Corresponding author
    1. Comparative Orthopedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, 601 Tharp Street, Columbus, Ohio 43210
    • Comparative Orthopedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, 601 Tharp Street, Columbus, Ohio 43210. Telephone: 614-292-6661
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Abstract

This study evaluated healing of equine metatarsal osteotomies and ostectomies in response to percutaneous injection of adenoviral (Ad) bone morphogenetic protein (BMP)-2, Ad-BMP-6, or beta-galactosidase protein vector control (Ad-LacZ) administered 14 days after surgery. Radiographic and quantitative computed tomographic assessment of bone formation indicated greater and earlier mineralized callus in both the osteotomies and ostectomies of the metatarsi injected with Ad-BMP-2 or Ad-BMP-6. Peak torque to failure and torsional stiffness were greater in osteotomies treated with Ad-BMP-2 than Ad-BMP-6, and both Ad-BMP-2- and Ad-BMP-6-treated osteotomies were greater than Ad-LacZ or untreated osteotomies. Gene expression of ostectomy mineralized callus 8 weeks after surgery indicated upregulation of genes related to osteogenesis compared to intact metatarsal bone. Expression of transforming growth factor beta-1, cathepsin H, and gelsolin-like capping protein were greater in Ad-BMP-2- and Ad-BMP-6-treated callus compared to Ad-LacZ-treated or untreated callus. Evidence of tissue biodistribution of adenovirus in distant organs was not identified by quantitative PCR, despite increased serum antiadenoviral vector antibody. This study demonstrated a greater relative potency of Ad-BMP-2 over Ad-BMP-6 in accelerating osteotomy healing when administered in this regimen, although both genes were effective at increasing bone at both osteotomy and ostectomy sites. © 2008 Orthopaedic Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:764–771, 2008

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