Mandu-Hrit Manuela, Seifert Erin, Kotsiopriftis Maria, Lauzier Dominique, Haque Tasima, Rohlicek Charles, Tabrizian Maryam, Hamdy Reggie C
Shriners Hospital for Children, Montreal, Canada.
Growth Factors. 2008 Jun;26(3):143-51. doi: 10.1080/08977190802106154.
We have previously shown that a single injection of rhBMP-7 (OP-1) applied to the regenerate early during distraction accelerates bone consolidation in a rabbit model of distraction osteogenesis. In the present study, we hypothesised that the injection of OP-1 improves bone consolidation by increasing blood flow to the distracted site. Blood flow into the regenerate of a rabbit model was measured and vascular endothelial growth factor (VEGF) expression was tested using semi-quantitative PCR. Immunohistochemistry was used for assessing the temporal and spatial expression of platelet endothelial cell adhesion molecule (PECAM), VEGF and its receptors following OP-1 injection. We observed a higher expression of VEGF and its receptors in the regenerate with OP-1 treatment. However, there was no difference in the increase in bone blood flow nor PECAM expression between the treated and control groups of animals. Interestingly, the increased expression of VEGF and its receptors was associated with chondrocyte and fibroblast-like cells, but not with endothelial cells. These results suggest that accelerated ossification by OP-1 may depend on a non-vascular mechanism, possibly involving a non-angiogenic function of VEGF signalling.
我们之前已经表明，在牵张成骨的兔模型中，在牵张早期单次注射重组人骨形态发生蛋白-7（OP-1）可加速骨愈合。在本研究中，我们假设注射OP-1通过增加牵张部位的血流量来改善骨愈合。测量了兔模型再生部位的血流量，并使用半定量PCR检测了血管内皮生长因子（VEGF）的表达。免疫组织化学用于评估注射OP-1后血小板内皮细胞黏附分子（PECAM）、VEGF及其受体的时空表达。我们观察到，OP-1治疗组再生部位VEGF及其受体的表达较高。然而，治疗组和对照组动物之间的骨血流量增加以及PECAM表达并无差异。有趣的是，VEGF及其受体表达的增加与软骨细胞和成纤维样细胞有关，而与内皮细胞无关。这些结果表明，OP-1加速骨化可能依赖于一种非血管机制，可能涉及VEGF信号传导的非血管生成功能。
