Angiogenesis is required for successful bone induction during distraction osteogenesis
Angiogenesis is required for successful bone induction during distraction osteogenesis
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DOI：
10.1359/jbmr.050301
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发表时间：
2005-07-01
影响因子：
6.2
通讯作者：
Longaker, MT
中科院分区：
文献类型：
--
作者：
Fang, TD;Salim, A;Longaker, MT
机械诱导骨形成过程中血管生成的作用还不完全清楚。在大鼠牵张成骨模型中确定了力学环境、血管生成和骨形成之间的关系。破坏机械环境或内皮细胞增殖阻断血管生成和骨形成。这项研究进一步定义了在牵引osteogenics.Introduction的机械环境和血管生成的作用：而成功的骨折修复需要一个协调和复杂的转录程序，整合mechanotransductive信号，血管生成和成骨，这些过程的相互依存关系还没有完全理解。在这项研究中，我们使用了一种被称为下颌骨牵张成骨（DO）的骨再生系统，在该系统中，在截骨术和截骨边缘逐渐分离后，受控的机械刺激促进骨诱导，以检查机械环境、血管生成和骨生成之间的关系。材料和方法：成年Sprague-Dawley大鼠接受渐进式牵引、渐进式牵引加血管生成抑制剂TNP-470或急性牵引（骨再生失败的模型）治疗。在牵张结束时（第13天）或巩固结束时（第41天）处死动物，并用μ CT、组织学和免疫组织化学检查血管生成和骨形成（每组每个时间点n = 4）。在第5、9、13、21和41天处理另外一组动物（每组每个时间点n = 6）用于微阵列分析。结果和结论：TNP-470施用或机械环境的破坏阻止正常的骨生成并导致纤维性骨不连。随后的再生分析显示，在未能愈合的组中，通过大体组织学和血小板内皮细胞粘附分子的免疫组织化学定位，没有血管生成。微阵列分析揭示了三组中与骨生成、血管生成和缺氧相关的基因表达的不同模式。我们的研究结果证实了机械环境，血管生成和成骨过程中DO的相互依赖性，并表明，诱导促血管生成基因和适当的机械环境都是必要的，以支持新的血管系统骨诱导DO。
The role of angiogenesis during mechanically induced bone formation is incompletely understood. The relationship between the mechanical environment, angiogenesis, and bone formation was determined in a rat distraction osteogenesis model. Disruption of either the mechanical environment or endothelial cell proliferation blocked angiogenesis and bone formation. This study further defines the role of the mechanical environment and angiogenesis during distraction osteogenesis.Introduction: Whereas successful fracture repair requires a coordinated and complex transcriptional program that integrates mechanotransductive signaling, angiogenesis, and osteogenesis, the interdependence of these processes is not fully understood. In this study, we use a system of bony regeneration known as mandibular distraction osteogenesis (DO) in which a controlled mechanical stimulus promotes bone induction after an osteotomy and gradual separation of the osteotomy edges to examine the relationship between the mechanical environment, angiogenesis, and osteogenesis.Materials and Methods: Adult Sprague-Dawley rats were treated with gradual distraction, gradual distraction plus the angiogenic inhibitor TNP-470, or acute distraction (a model of failed bony regeneration). Animals were killed at the end of distraction (day 13) or at the end of consolidation (day 41) and examined with mu CT, histology, and immunohistochemistry for angiogenesis and bone formation (n = 4 per time-point per group). An additional group of animals (n = 6 per time-point per group) was processed for microarray analysis at days 5, 9, 13, 21, and 41.Results and Conclusions: Either TNP-470 administration or disruption of the mechanical environment prevented normal osteogenesis and resulted in a fibrous nonunion. Subsequent analysis of the regenerate showed an absence of angiogenesis by gross histology and immunohistochemical localization of platelet endothelial cell adhesion molecule in the groups that failed to heal. Microarray analysis revealed distinct patterns of expression of genes associated with osteogenesis, angiogenesis, and hypoxia in each of the three groups. Our findings confirm the interdependence of the mechanical environment, angiogenesis, and osteogenesis during DO, and suggest that induction of proangiogenic genes and the proper mechanical environment are both necessary to support new vasculature for bone induction in DO.