rhBMP-2 Modulation of Gene Expression in Infected Segmental Bone Defects

• Published in: Clinical orthopaedics and related research 2009-12, Vol.467 (12), p.3096-3103
• Main Authors: Brick, Katherine E., Chen, Xinqian, Lohr, Jamie, Schmidt, Andrew H., Kidder, Louis S., Lew, William D.
• Format: Article
• Language: English
• Subjects: Animals; Bone Diseases, Infectious - drug therapy; Bone Diseases, Infectious - genetics; Bone Diseases, Infectious - microbiology; Bone Diseases, Infectious - physiopathology; Bone Morphogenetic Protein 2 - administration & dosage; Bone Morphogenetic Protein Receptors, Type II - genetics; Bone Remodeling - drug effects; Bone Remodeling - genetics; Collagen Type I - genetics; Collagen Type II - genetics; Conservative Orthopedics; Disease Models, Animal; Drug Carriers; Femoral Fractures - drug therapy; Femoral Fractures - genetics; Femoral Fractures - microbiology; Femoral Fractures - physiopathology; Femur - drug effects; Femur - metabolism; Femur - microbiology; Femur - surgery; Fracture Healing - drug effects; Fracture Healing - genetics; Humans; Medicine; Medicine & Public Health; Orthopedics; Osteocalcin - genetics; Rats; Rats, Sprague-Dawley; Recombinant Proteins - administration & dosage; RNA, Messenger - metabolism; Sports Medicine; Staphylococcal Infections - drug therapy; Staphylococcal Infections - genetics; Staphylococcal Infections - microbiology; Staphylococcal Infections - physiopathology; Staphylococcus aureus - pathogenicity; Surgery; Surgical Orthopedics; Surgical Sponges; Symposium: Tribute to Dr. Marshall Urist: Musculoskeletal Growth Factors; Time Factors; Up-Regulation
• ISSN: 0009-921X; 1528-1132
• DOI: 10.1007/s11999-008-0599-3

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.