rhBMP-2 Modulation of Gene Expression in Infected Segmental Bone Defects |
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Authors: | Katherine E Brick Xinqian Chen Jamie Lohr Andrew H Schmidt Louis S Kidder William D Lew |
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Institution: | (1) Midwest Orthopaedic Research Foundation, Minneapolis, MN, USA;(2) Division of Pediatric Cardiology, Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN, USA;(3) Orthopaedic Surgery Department, Hennepin County Medical Center, Minneapolis, MN, USA;(4) Department of Radiology, University of Minnesota School of Medicine, B292 Mayo, 420 Delaware Street SE, Minneapolis, MN 55455, USA; |
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Abstract: | The osteoinductive capability of BMPs appears diminished in the setting of acute infection. We applied rhBMP-2 to a segmental
defect in a rat femur and measured the expression of key bone formation genes in the presence of acute infection. Types I
and II collagen, osteocalcin, and BMP Type II receptor mRNA expression were characterized in 72 Sprague-Dawley rats, which
received either bovine collagen carrier with 200 μg rhBMP-2 plus Staphylococcus aureus, carrier with bacteria only, carrier
with rhBMP-2 only, or carrier alone. Six animals from each group were euthanized at 1, 2, and 4 weeks. Total RNA was isolated
and extracted, and mRNA was determined by real-time comparative quantitative PCR. Infected defects had little expression of
collagen I and II and osteocalcin mRNAs, while BMP receptor II expression with infection was greater than carrier-only controls
at Weeks 2 and 4. Notably, all four genes were upregulated in infected defects in the presence of rhBMP-2. Thus, in a clinical
setting with a high risk of infection and nonunion, such as a compound fracture with bone loss, rhBMP-2 may increase the rate
and extent of bone formation. Even if infection does occur, rhBMP-2 may allow a quicker overall recovery time. |
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