Abstract

Quantitative gene expression analysis and immunohistochemistry were used to investigate the temporal and spatial expression of bone morphogenic proteins (BMPs) and BMP antagonists in a posterolateral spine fusion model in rabbits. To identify the expression pattern of BMPs and BMP antagonists and to determine the molecular and histologic changes of the graft and surrounding tissue during fusion. There are no studies on BMP antagonists during spinal fusion. Furthermore, the reciprocal interaction between bone grafts and surrounding tissue is still unknown in fusion. Eighteen New Zealand White rabbits underwent bilateral posterolateral spine fusion with autogenous bone graft. Rabbits were killed at 1, 2, 4, or 6 weeks after arthrodesis. The spinal fusions were analyzed by radiography. On the right side, specimens were collected from the outer zone over the transverse processes, the inner zone between the transverse processes, muscle surrounding bone grafts, and the transverse process. Gene expression of BMP-2, BMP-4, and BMP-7, noggin, chordin, Sox9, and Runx2 were measured by real-time polymerase chain reaction at each time point of each sample. On the left side, molecules of interest were evaluated by immunohistochemistry on tissue sections. BMP-2, BMP-4, and BMP-7, noggin, and chordin were colocalized in rimming osteoblasts, osteoclasts, and chondrocytes. The outer zone demonstrated earlier bone maturation and faster increase in BMP gene expression than the inner zone. Muscle surrounding bone grafts showed significantly higher BMP expression and Runx2 activity at the early phase. BMP-positive cells were also noted around blood vessels. The colocalization and temporal relationship of BMPs and BMP antagonists suggests that BMP activity is tightly regulated by the antagonists during fusion. In addition, not only the decorticated transverse process, but also muscle surrounding bone grafts, is actively involved in osteogenesis during fusion.

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