Journal Article

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

Kidder, Louis S., Chen, Xinqian, Lohr, Jamie, Schmidt, Andrew H., Brick, Katherine E., Lew, William D.

2009

Overview

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.

• Publisher: Springer-Verlag,Lippincott Williams & Wilkins Ovid Technologies
• Subject: 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