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.
Abstract: 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: 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.
© Copyright 2012 by The American College of Veterinary Surgeons.
Publication Date: 2012-02-06 PubMed ID: 22308976DOI: 10.1111/j.1532-950X.2011.00947.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research study tested gene transfer within horses using adenoviral vectors encoding human bone morphogenetic protein-2 and -7. As the result, the team found that there was no significant improvement in bone healing in treated horses after 16 weeks.
Study Design and Procedures
- The study involved 15 healthy adult horses which were divided into three groups with 5 horses each.
- An ostectomy (a surgical procedure to remove a segment of bone) was performed on each horse to create a defect for healing study.
- Post-surgery, the horses received either an adenoviral vector encoding human bone morphogenetic protein-2 and -7 (Ad-hBMP-2/-7) or an adenoviral vector encoding a green fluorescent protein (Ad-GFP) injected into the ostectomy sites.
- Each horse received the same treatment on both left and right forelimbs.
- A separate group of five horses did not receive any treatment and were used as controls.
- Bone healing was monitored periodically using X-ray and other imaging technologies for 16 weeks.
Results of the Study
- The group of horses that received the Ad-GFP treatment displayed lower rates of bone ossification compared to the untreated control group at the 4 and 6 week marks.
- There was no noticeable difference in the healing between the group that received the Ad-hBMP-2/-7 treatment and the untreated control group at any measured point.
- At the end of the 16-week study, no significant difference in bone healing was found across all groups–treated and untreated–when evaluated radiographically, histologically, or using DEXA.
Conclusions of the Study
- The use of Ad-hBMP-2/-7 did not result in any improvement in bone healing in the treated horses at the end of the 16-week study period.
Given these results, the study suggests that further research may be necessary to identify more effective gene transfer methods or alternative therapeutic agents for improving bone healing in equine models.
Cite This Article
APA
Southwood LL, Kawcak CE, Hidaka C, McIlwraith CW, Werpy N, Macleay J, Frisbie DD.
(2012).
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, 41(3), 345-354.
https://doi.org/10.1111/j.1532-950X.2011.00947.x Publication
Researcher Affiliations
- Department of Clinical Studies, New Bolton Center, University of Pennsylvania, Kennett Square, PA 19348, USA. southwoo@vet.upenn.edu
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
Citations
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