Temporal and spatial expression of bone morphogenetic protein-2,-4, and-7 during distraction osteogenesis in rabbits

The Ilizarov method of limb lengthening makes use of the fact that osteogen esis is induced at an osteotomy site when distraction is applied. It is unk nown at present how the mechanical forces created by distraction are transl ated into biological signals. Because bone morphogenetic proteins (BMPs) ar e potent inducers of osteogenesis in many experimental systems, they are ob vious candidates for playing a role in this process. In this study, we inve stigated the temporal and spatial expression of BMP-2, -4, and -7 proteins during distraction osteogenesis using immunohistochemistry. An osteotomy wa s performed on the right tibiae of white New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 h for 3 weeks, followed by a 3 week, consolidation phase. Each week after osteotomy one ra bbit was killed for immunohistochemical studies. Staining for BMP-2, -4, an d -7 was evident before distraction was applied and was mainly localized to mesenchymal cells and osteoblastic cells in the periosteal region. After d istraction was started, the typical fibrous interzone developed between the osteotomy fragments, where both intramembranous and endochondral ossificat ion were noted, In this area, cells resembling fibroblasts and chondrocytes , but not mature osteoblasts, showed intense staining for all three BMPs. T his high level of expression was maintained during the entire distraction p hase and then gradually disappeared during the consolidation phase. These r esults are compatible with the hypothesis that BMPs play an important role in the signaling pathways that. link the mechanical forces created by distr action to biological responses. (Bone 26:611-617; 2000) (C) 2000 by Elsevie r Science Inc. All rights reserved.