Assessing the role of bone morphogenetic protein-2 (BMP2) in vessel formation during distraction osteogenesis
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Bone Morphogenetic Protein 2 (BMP2) is a growth factor needed to initiate fracture repair and is involved in the differentiation of progenitor cells to the osteochondral lineage. Osteogenesis and angiogenesis are coupled processes, however the mechanism by which these processes are coupled and the role that BMP2 plays in coupling these processes is not well understood. In distraction osteogenesis, a bone regeneration model mediated by mechanical distraction of an osteotomy, BMP2 expression was primarily associated with blood vessels. Therefore, transgenic mice were used to conditionally delete BMP2 expression (BMP2-cKO) in smooth muscle cells during distraction osteogenesis to identify the role of BMP2 in osteogenesis and angiogenesis. Vessel formation was characterized by vascular perfusion of animals with a barium-gelatin solution, which was used as a radiographic contrast agent that allowed vessel formation to be quantified by micro-computer assisted tomography (µCT). Using the same transgenic mice to label those cells in which BMP2 had been deleted, histological analysis was performed to confirm the targeting specificity of the BMP2-cKO. µCT analysis showed less bone formation occurred in the BMP2-cKO animals compared to controls. The µCT analysis further showed vessel volume and thickness were decreased in BMP2-cKO animals at both day 17 and 31, suggesting that there is a relationship between BMP2 and vessel size. Vessel number was greater in controls than the BMP2-cKO animals at day 17, however the BMP2-cKO animals had a larger vessel number than the number by day 31. Histological analysis confirmed knockout of BMP2 expression in smooth muscle cells, as well as in skeletal muscle and chondrocytes. These results suggest the importance of BMP2, not only in bone formation, but also in vessel morphogenesis.