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

Authors


  • Funded in part by the Grayson Jockey Club Research Foundation. Work completed at the Equine Orthopaedic Research Center, Colorado State University. Thanks to Dr. Julie Engiles for assistance with histological education.

Corresponding Author

Louise L. Southwood, BVSc, PhD, Diplomate ACVS, Diplomate ACVECC, Department of Clinical Studies, New Bolton Center, 382 West Street Rd, Kennett Square, PA 19348

E-mail: southwoo@vet.upenn.edu

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).

Study Design

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.

Ancillary