Osteogenic gene regulation and relative acceleration of healing by adenoviral-mediated transfer of human BMP-2 or -6 in equine osteotomy and ostectomy models.
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.
Ishihara
Akikazu
A
Comparative Orthopedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, 601 Tharp Street, Columbus, Ohio 43210, USA.
Shields
Kathleen M
KM
Litsky
Alan S
AS
Mattoon
John S
JS
Weisbrode
Steven E
SE
Bartlett
Jeffrey S
JS
Bertone
Alicia L
AL
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002146:Bony Callus / Q000000981:diagnostic imaging / Q000503:physiopathology; D004195:Disease Models, Animal; D017102:Fracture Healing / Q000235:genetics*; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006736:Horses; D006801:Humans; D007763:Lac Operon; D008682:Metatarsal Bones / Q000000981:diagnostic imaging / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis / Q000235:genetics*; D010027:Osteotomy; D014057:Tomography, X-Ray Computed; D019415:Torque; D054159:Torsion, Mechanical; D016212:Transforming Growth Factor beta / Q000235:genetics*
C525718:BMP2 protein, human; C525816:BMP6 protein, human; D055396:Bone Morphogenetic Protein 2; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta