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

Vet Surg. 2012 Apr;41(3):345-54. doi: 10.1111/j.1532-950X.2011.00947.x. Epub 2012 Feb 6.

Abstract

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).

Experimental animals: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon / veterinary
  • Animals
  • Bone Morphogenetic Protein 2 / genetics*
  • Bone Morphogenetic Protein 7 / genetics*
  • Bone Regeneration / physiology*
  • Gene Transfer Techniques / veterinary*
  • Genetic Vectors / genetics
  • Horses / surgery
  • Male
  • Metacarpal Bones / diagnostic imaging
  • Metacarpal Bones / pathology
  • Metacarpal Bones / physiology*
  • Metacarpal Bones / surgery

Substances

  • BMP2 protein, human
  • BMP7 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 7