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Home / Equine Research Bank / Osteoarthritis Cartilage / Direct delayed human adenoviral BMP-2 or BMP-6 gene therapy ...
Osteoarthritis and cartilage2011; 19(8); 1066-1075; doi: 10.1016/j.joca.2011.05.007

Direct delayed human adenoviral BMP-2 or BMP-6 gene therapy for bone and cartilage regeneration in a pony osteochondral model.

Abstract: To evaluate healing of surgically created large osteochondral defects in a weight-bearing femoral condyle in response to delayed percutaneous direct injection of adenoviral (Ad) vectors containing coding regions for either human bone morphogenetic proteins 2 (BMP-2) or -6. Methods: Four 13mm diameter and 7mm depth circular osteochondral defects were drilled, 1/femoral condyle (n=20 defects in five ponies). At 2 weeks, Ad-BMP-2, Ad-BMP-6, Ad-green fluorescent protein (GFP), or saline was percutaneously injected into the central drill hole of the defect. Quantitative magnetic resonance imaging (qMRI) and computed tomography (CT) were serially performed at 12, 24, and 52 weeks. At 12 (one pony) or 52 weeks, histomorphometry and microtomographic analyses were performed to assess subchondral bone and cartilage repair tissue quality. Results: Direct delivery of Ad-BMP-6 demonstrated delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and histologic evidence of greater Glycosaminoglycan (GAG) content in repair tissue at 12 weeks, while Ad-BMP-2 had greater non-mineral cartilage at the surface at 52 weeks (p<0.04). Ad-BMP-2 demonstrated greater CT subchondral bone mineral density (BMD) by 12 weeks and both Ad-BMP-2 and -6 had greater subchondral BMD at 52 weeks (p<0.05). Despite earlier (Ad-BMP-6) and more persistent (Ad-BMP-2) chondral tissue and greater subchondral bone density (Ad-BMP-2 and -6), the tissue within the large weight-bearing defects at 52 weeks was suboptimal in all groups due to poor quality repair cartilage, central fibrocartilage retention, and central bone cavitation. Delivery of either BMP by this method had greater frequency of subchondral bone cystic formation (p<0.05). Conclusions: Delivery of Ad-BMP-2 or Ad-BMP-6 via direct injection supported cartilage and subchondral bone regeneration but was insufficient to provide long-term quality osteochondral repair.
Published by Elsevier Ltd.
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Publication Date: 2011-06-02 PubMed ID: 21683796DOI: 10.1016/j.joca.2011.05.007Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article evaluates the use of percutaneous direct injection of gene therapy to encourage bone and cartilage regeneration in large osteochondral defects. However, despite initial healing progress, the long-term repair quality was suboptimal for the established testing conditions.

Objective of the Research

  • The study aimed at examining the efficacy of gene therapy in the healing of large osteochondral defects specifically in a weight-bearing femoral condyle. This was achieved by injecting adenoviral (Ad) vectors containing coding regions for either human bone morphogenetic proteins 2 (BMP-2) or -6 (BMP-6) into the postsurgical defects.

Methodology

  • The study was carried out in five ponies; four osteochondral defects of 13mm diameter and 7mm depth were drilled into each femoral condyle.
  • Two weeks after the surgery, they were divided to receive percutaneously an injection of Ad-BMP-2, Ad-BMP-6, Ad-green fluorescent protein (GFP), or saline into the central drill hole of the defect.
  • The healing and regeneration of the defects were then monitored for 52 weeks through quantitative magnetic resonance imaging (qMRI) and computed tomography (CT).
  • Histomorphometry and microtomographic analyses were performed at weeks 12 and 52 to assess the quality of bone and cartilage repair tissue.

Results and Interpretation

  • Both Ad-BMP-2 and Ad-BMP-6 displayed evidence of cartilage and subchondral bone regeneration, but with variations. Ad-BMP-6 showed superior repair tissue quality in terms of Glycosaminoglycan (GAG) content at 12 weeks, while Ad-BMP-2 displayed greater non-mineral cartilage at the surface at 52 weeks.
  • Ad-BMP-2 demonstrated superior subchondral bone mineral density (BMD) by 12 weeks, while both Ad-BMP-2 and -6 exhibited greater BMD at 52 weeks.
  • However, despite these positive outcomes, the overall quality of tissue repair within the large weight-bearing defects at 52 weeks was below expectation. This was due to poor quality repair cartilage, central fibrocartilage retention, and central bone cavitation.
  • Another downside was the increased occurrence of subchondral bone cystic formation with the delivery of either BMP by the chosen method.

Conclusion

  • The study underscored that the direct delivery of Ad-BMP-2 or Ad-BMP-6 did support cartilage and subchondral bone regeneration in large osteochondral defects. However, the poor long-term quality of osteochondral repair under the trialed conditions called for further refinement and optimization of the treatment approach.

Cite This Article

APA
Menendez MI, Clark DJ, Carlton M, Flanigan DC, Jia G, Sammet S, Weisbrode SE, Knopp MV, Bertone AL. (2011). Direct delayed human adenoviral BMP-2 or BMP-6 gene therapy for bone and cartilage regeneration in a pony osteochondral model. Osteoarthritis Cartilage, 19(8), 1066-1075. https://doi.org/10.1016/j.joca.2011.05.007

Publication

Osteoarthritis and cartilage
ISSN: 1522-9653
NlmUniqueID: 9305697
Country: England
Language: English
Volume: 19
Issue: 8
Pages: 1066-1075

Researcher Affiliations

Menendez, M I
  • Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Clark, D J
    Carlton, M
      Flanigan, D C
        Jia, G
          Sammet, S
            Weisbrode, S E
              Knopp, M V
                Bertone, A L

                  MeSH Terms

                  • Adenoviridae / genetics
                  • Animals
                  • Bone Density
                  • Bone Morphogenetic Protein 2 / pharmacology
                  • Bone Morphogenetic Protein 2 / therapeutic use
                  • Bone Morphogenetic Protein 6 / pharmacology
                  • Bone Morphogenetic Protein 6 / therapeutic use
                  • Bone Regeneration / drug effects
                  • Bone Regeneration / physiology
                  • Cartilage, Articular / drug effects
                  • Cartilage, Articular / metabolism
                  • Cartilage, Articular / pathology
                  • Disease Models, Animal
                  • Femur / physiology
                  • Gadolinium DTPA
                  • Genetic Therapy / methods
                  • Genetic Vectors / administration & dosage
                  • Glycosaminoglycans / metabolism
                  • Green Fluorescent Proteins / metabolism
                  • Hindlimb / physiology
                  • Horses
                  • Humans
                  • Magnetic Resonance Imaging / methods
                  • Tomography, X-Ray Computed
                  • Weight-Bearing

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