Evaluation of direct in vivo gene transfer in an equine metacarpal IV ostectomy model using an adenoviral vector encoding the bone morphogenetic protein-2 and protein-7 gene.
OBJECTIVE
To evaluate gene transfer in an equine metacarpal IV (MCIV) ostectomy model using adenoviral vectors encoding the human bone morphogenetic protein-2 and protein-7 gene (Ad-BMP-2/-7).


METHODS



METHODS
Healthy adult horses (n = 15).


METHODS
A plate stabilized, critical size 1.5 cm ostectomy was created in left and right MCIV. The ostectomy site was injected with either Ad-green fluorescent protein (Ad-GFP) or Ad-hBMP-2/-7 at completion of surgery; the same treatment was assigned to both the left and right forelimb of each horse (n = 5 horses/group). Bone healing was evaluated radiographically every 2 weeks for 16 weeks. Horses in a pilot study (n = 5) were used as untreated controls for radiographic evaluation to 8 weeks. After euthanasia at 16 weeks bone healing was evaluated using dual energy X-ray absorptiometry (DEXA) and histomorphometry. Data were analyzed using an ANOVA or Kruskal-Wallis test. Level of significance was P < .05.


RESULTS
At 4 and 6 weeks, the Ad-GFP group had a significantly lower percentage defect ossification compared with the untreated control group. There was no significant difference between untreated and Ad-hBMP-2/-7 groups at any time point and no significant difference in bone healing radiographically, histologically, or using DEXA between any groups at 16 weeks.


CONCLUSIONS
Ad-hBMP-2/-7 did not improve bone healing in horses at 16 weeks.
Department of Clinical Studies, New Bolton Center, University of Pennsylvania, Kennett Square, PA 19348, USA. southwoo@vet.upenn.edu
Louise L
LL
Southwood
Christopher E
CE
Kawcak
Chisa
C
Hidaka
C Wayne
CW
McIlwraith
Natasha
N
Werpy
Jennifer
J
Macleay
David D
DD
Frisbie
D015502:Absorptiometry, Photon / Q000662:veterinary; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics*; D001861:Bone Regeneration / Q000502:physiology*; D018014:Gene Transfer Techniques / Q000662:veterinary*; D005822:Genetic Vectors / Q000235:genetics; D006736:Horses / Q000601:surgery; D008297:Male; D050279:Metacarpal Bones / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology* / Q000601:surgery
C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7