Expression of bone morphogenetic proteins during membranous bone healing

tk:2For the reconstructive plastic surgeon, knowledge of the molecular biol ogy underlying membranous fracture healing is becoming increasingly vital. Understanding the complex patterns of gene expression manifested during the course of membranous fracture repair will be crucial to designing therapie s that augment poor fracture healing or that expedite normal osseous repair by strategic manipulation of the normal course of gene expression. Sn the current study, ive present a rat model of membranous bone repair. This mode l has great utility because of its technical simplicity, reproducibility, a nd relatively low cost. Furthermore, it is a powerful tool for analysis of the molecular regulation of membranous bone repair by immunolocalization an d/or in situ hybridization techniques. In this study, an osteotomy was made within the caudal half of the hemimand ible, thus producing a stable bone defect without the need for external or internal fixation. The healing process was then catalogued histologically i n 28 Sprague-Dawley rats that were serially killed at 1, 2, 3, 4, 5, 6, and 8 weeks after operation. Furthermore, using this novel model, we analyzed, within the context of membranous bone healing, the temporal and spatial ex pression patterns of several members of the bone morphogenetic protein (BMP ) family, known to be critical regulators of cells of osteoblast Lineage. O ur data suggest that BMP-2/-4 and BMP-7, also known as osteogenic protein-1 (OP-1), are expressed by osteoblasts, osteoclasts, and other more primitiv e mesenchymal cells within the fracture callus during the early stages of m embranous fracture healing. These proteins continue to be expressed during the process of bone remodeIing, albeit less prominently. The return of BMP- 2/-4 and OP-1 immunostaining to baseline intensity coincides with the histo logical appearance of mature lamellar bone. Taken together, these data unde rscore the potentially important regulatory role played by the bone morphog enetic proteins in the process of membranous bone repair.