rhBMP-2 modulation of gene expression in infected segmental bone defects.
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 mug 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.
Brick
Katherine E
KE
Midwest Orthopaedic Research Foundation, Minneapolis, MN, USA.
Chen
Xinqian
X
Lohr
Jamie
J
Schmidt
Andrew H
AH
Kidder
Louis S
LS
Lew
William D
WD
D000818:Animals; D001850:Bone Diseases, Infectious / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology / Q000503:physiopathology; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics; D016723:Bone Remodeling / Q000187:drug effects* / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics; D004195:Disease Models, Animal; D004337:Drug Carriers; D005264:Femoral Fractures / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology / Q000503:physiopathology; D005269:Femur / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000601:surgery; D017102:Fracture Healing / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015675:Osteocalcin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000472:pathogenicity; D015503:Surgical Sponges; D013997:Time Factors; D015854:Up-Regulation
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D024043:Collagen Type II; D004337:Drug Carriers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015675:Osteocalcin; D052006:Bone Morphogenetic Protein Receptors, Type II