Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Aug;19(8):1066-75.
doi: 10.1016/j.joca.2011.05.007. Epub 2011 Jun 2.

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

M I Menendez  1 , D J Clark, M Carlton, D C Flanigan, G Jia, S Sammet, S E Weisbrode, M V Knopp, A L Bertone
Affiliations
Free article

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

M I Menendez et al. Osteoarthritis Cartilage. 2011 Aug.
Free article

Abstract

Objective: 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.

PubMed Disclaimer

Publication types

MeSH terms

LinkOut - more resources