Gene Expression for Type-Specific Collagens in Osteogenic Protein-1 (rhBMP-7)-Induced Lumbar Intertransverse Process Fusion in Rabbits

Abstract

To elucidate the molecular mechanism by which osteogenic protein (OP)-1 induces posterolateral lumbar spine fusion (PLF), we analyzed the process of OP-1-induced PLF in an established rabbit model by means of in situ hybridization (ISH). Intertransverse process lumbar fusions were performed at L5-L6 in rabbits using OP-1 (n = 18) or carrier alone (n = 9). The vertebrae were harvested at 2, 4, and 6 weeks postsurgery, and fusion masses evaluated using radiography, histology and ISH. In the OP-1 group, a contiguous fusion mass bridged the L5 and L6 transverse processes by 6 weeks postsurgery. At 2 weeks, collagen types II and X were expressed both near the transverse process and at the central portion of the intertransverse process area, corresponding to abundant, multifocal cartilage. After 4 weeks, endochondral ossification progressed from the transverse process toward the central portion. At 6 weeks, genes for collagen types II and X were restricted at the front of endochondral ossification. In carrier-alone group, no fusion mass was formed. The results demonstrate that OP-1 vigorously stimulates cells and induces chondrogenesis in the early phase of PLF. In the late phase, however, endochondral bone formation progressing toward the central portion became the major process, as was observed in PLF with autograft. In OP-1-induced PLF, therefore, osteogenic action of OP-1 seems to be quite intensive in the early phase but not in the late phase.