The Marshall R. Urist Young Investigator Award. Gene expression during autograft lumbar spine fusion and the effect of bone morphogenetic protein 2.
A prospective animal study of posterolateral lumbar spine arthrodesis was performed to determine the temporal and spatial pattern of gene expression and to determine the effect of recombinant human bone morphogenetic protein 2 on the gene expression pattern of a healing spine fusion mass. In Group 1, 20 adult New Zealand rabbits underwent L4-L5 posterolateral intertransverse process arthrodesis using autograft alone. Two rabbits were euthanized at each of the following points: 0, 2, and 4 days, and 1, 2, 3, 4, 5, 6, and 10 weeks after surgery. The same surgical technique was used for 16 rabbits in Group II, except that the autograft first was soaked in a solution of recombinant human bone morphogenetic protein 2 before implantation. Ribonucleic acid was extracted from different regions of the fusion mass at each point and analyzed for expression of bone and cartilage related genes using reverse transcription polymerase chain reaction. A reproducible temporal sequence and spatial pattern of gene expression was found in healing spine fusions. In the central portion of the fusion mass a temporal lag in gene expression was observed that parallels the lag in healing within the central zone previously observed in histologic studies. Treatment of bone graft with recombinant human bone morphogenetic protein 2 resulted in an increase in the early expression of bone morphogenetic protein 6 which was associated with expression of higher levels of Type I collagen, osteocalcin, and other bone related genes. These findings suggest that central nonunion may be associated with delayed expression of osteoblast related genes in the central region of the forming fusion mass. The growth factor, recombinant human bone morphogenetic protein 2, increased the level of bone related gene expression throughout the fusion mass, eliminated the delay in healing within the central zone, and may decrease the likelihood of a nonunion.
Morone
M A
MA
Emory Spine Center, Department of Orthopaedics, Emory University School of Medicine, Atlanta, GA 30033, USA.
Boden
S D
SD
Hair
G
G
Martin
G J
GJ
Racine
M
M
Titus
L
L
Hutton
W C
WC
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D016025:Bone Transplantation / Q000379:methods; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008159:Lumbar Vertebrae / Q000601:surgery*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013123:Spinal Fusion / Q000379:methods; D013997:Time Factors; D016212:Transforming Growth Factor beta; D014182:Transplantation, Autologous; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2