Healing of non-displaced fractures produced by fatigue loading of the mouse ulna.
Healing of non-displaced fractures produced by fatigue loading of the mouse ulna.
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DOI：
10.1016/j.bone.2010.02.030
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发表时间：
2010-06
期刊：
影响因子：
4.1
通讯作者：
Silva, Matthew J.
中科院分区：
文献类型：
--
作者：
Martinez, Mario D.;Schmid, Gregory J.;McKenzie, Jennifer A.;Ornitz, David M.;Silva, Matthew J.
我们开发了一种疲劳负荷方案，在小鼠体内产生非移位尺骨骨折，并表征了早期愈合反应。使用成年（5个月）C57 Bl/6小鼠，我们首先确定在负载控制下前肢的循环压缩会导致施加的位移增加，并最终导致完全骨折。然后，我们对80只小鼠的右前肢施加循环载荷（2 Hz;峰值力~4 N），并将位移限制在0.75 mm（完全骨折时平均位移的60%）。该疲劳方案通过尺骨中段附近的内侧皮质产生部分非移位性骨折，并使尺骨强度和刚度降低> 50%。在1天内，有显着的上调基因相关的缺氧（HIF 1a）和成骨（Bmp 2，BSP）在负载尺骨相比，非负载，对侧控制。基因表达反应在第7天附近达到峰值（例如，Osx上调8倍），并且包括FGF家族基因的上调（例如，Fgfr 3上涨6倍）。组织学上，在骨折部位观察到局部骨膜反应;到第7天，软骨区域周围有丰富的骨膜编织骨。从第7天到第14天，编织骨变得更致密，但面积没有增加。到第14天，编织骨反应导致尺骨强度和刚度完全恢复，机械性能恢复到正常水平。在未来，疲劳加载方法可用于在转基因和基因敲除小鼠中产生非移位性骨折，以研究骨骼快速修复损伤的机制。
We developed a fatigue loading protocol in mice to produce a non-displaced ulnar fracture in vivo, and characterized the early healing response. Using adult (5 mo) C57Bl/6 mice, we first determined that cyclic compression of the forelimb under load-control leads to increasing applied displacement and, eventually, complete fracture. We then subjected the right forelimbs of 80 mice to cyclic loading (2 Hz; peak force ~4 N) and limited the displacement to 0.75 mm (60% of the average displacement at complete fracture). This fatigue protocol created a partial, non-displaced fracture through the medial cortex near the ulnar mid-shaft, and reduced ulnar strength and stiffness by >50%. Within 1 day, there was significant upregulation of genes related to hypoxia (Hif1a) and osteogenesis (Bmp2, Bsp) in loaded ulnae compared to non-loaded, contralateral controls. The gene expression response peaked in magnitude near day 7 (e.g., Osx upregulated 8-fold), and included upregulation of FGF-family genes (e.g., Fgfr3 up 6-fold). Histologically, a localized periosteal response was seen at the site of the fracture; by day 7 there was abundant periosteal woven bone surrounding a region of cartilage. From days 7 to 14, the woven bone became denser but did not increase in area. By day 14, the woven-bone response resulted in complete recovery of ulnar strength and stiffness, restoring mechanical properties to normal levels. In the future, the fatigue loading approach can be used create non-displaced bone fractures in transgenic and knockout mice to study the mechanisms by which the skeleton rapidly repairs damage.
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