COMP-angiopoietin-1 accelerates bone formation during distraction osteogenesis

Introduction: During distraction osteogenesis, new and highly vascularized bone is formed, with angiogenesis preceding osteogenesis. We investigated the possibility that COMP-Ang1, an angiogenic factor, may facilitate bone formation. Methods: Rats were divided into three groups. Control rats underwent tibial distraction without treatment. In the two remaining groups, BSA (100 mu g) or COMP-Ang1 (100 mu g) were injected transcutaneously into the center of the distraction zone. Using radiographic and histologic analyses, we assessed total bone volume, vascular density, and bone mineral density. Total RNA was prepared from regenerated bone and analyzed for osteogenic marker protein expression using real-time RT-PCR analysis. Results: Bone formation in the distraction gap progressed more quickly in the COMP-Ang1-treated group than in the BSA-treated group. Histological findings and immunostaining of endothelial cells for factor VIII revealed that Comp-Ang1 group animals exhibited higher levels of vascularity. NanoCT and dual-energy X-ray absorptiometry analyses revealed increased new bone formation along capillaries in the COMP-Ang1 group compared with the BSA group. Runt-related transcription factor 2 and its target genes, including bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the COMP-Ang1 group. Conclusions: Our results are consistent with previous descriptions of the positive relationship between angiogenesis and osteogenesis. In addition, our results suggest the potential use of COMP-Ang1 as a therapeutic agent for treatment of distracted limbs by enhancing angiogenesis. (C) 2010 Elsevier Inc. All rights reserved.