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 ex pression and to determine the effect of recombinant human bone morphog enetic protein 2 on the gene expression pattern of a healing spine fus ion mass. In Group 1, 20 adult New Zealand rabbits underwent L4-L5 pos terolateral intertransverse process arthrodesis using autograft alone. Two rabbits were euthanized at each of the following points: 0, 2, an d 4 days, and 1, 2, 3, 4, 5, 6, and 10 weeks after surgery. The same s urgical technique was used for 16 rabbits in Group II, except that the autograft first was soaked in a solution of recombinant human bone mo rphogenetic protein 2 before implantation. Ribonucleic acid was extrac ted from different regions of the fusion mass at each point and analyz ed for expression of bone and cartilage related genes using reverse tr anscription polymerase chain reaction. A reproducible temporal sequenc e and spatial pattern of gene expression was found in healing spine fu sions. In the central portion of the fusion mass a temporal lag in gen e 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 resulte d in an increase in the early expression of bone morphogenetic protein 6 which was associated with expression of higher levels of Type I col lagen, osteocalcin, and other bone related genes. These findings sugge st that central nonunion may be associated with delayed expression of osteoblast related genes in the central region of the forming fusion m ass. The growth factor, recombinant human bone morphogenetic protein 2 , increased the level of bone related gene expression throughout the f usion mass, eliminated the delay in healing within the central zone, a nd may decrease the likelihood of a nonunion.