Characterization of a closed femur fracture model in mice
Characterization of a closed femur fracture model in mice
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DOI：
10.1097/00005131-200411000-00006
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发表时间：
2004-11-01
影响因子：
2.3
通讯作者：
O'Connor, JP
中科院分区：
文献类型：
--
作者：
Manigrasso, MB;O'Connor, JP
目的：本研究的目的是开发和表征一个封闭的小鼠股骨骨折模型，可用于骨折愈合的分子和遗传分析。研究设计：纵向时间研究的物种特异性fracture healing.Methods：一个协议，开发用于创建可重复的，封闭的小鼠股骨骨折。通过将0.01英寸直径的不锈钢丝逆行插入髓腔来稳定即将发生的骨折。用30号针的前2 mm制成的楔形物将髓内针固定在适当位置。通过3点弯曲产生骨折。通过X线片评估骨折愈合情况。结果：小鼠股骨骨折技术产生了良好的结果，动物损失最小。在研究中使用的246只小鼠中，22只小鼠由于骨折质量差（8只）、骨折稳定性丧失（6只）或麻醉死亡（8只）而被排除。放射摄影显示小鼠之间骨折愈合的一致模式，在骨折后10天（15只小鼠）至14天（18只小鼠）具有明显的峰值骨折骨痂体积。骨折桥接在所有3周骨折后X线片（35只小鼠）中均明显。117例标本在9个时间点的组织学检查显示骨折后7天骨折骨痂内软骨细胞分化，骨折后10天发生软骨内骨化，骨折后3周骨重建明显。尽管3周后有骨折桥接的放射学和组织学证据，但68只小鼠在骨折后3、4、6和12周的扭转力学测试显示，（每个时间点在冰中的组大小为15至18）表明直到骨折后6至12周才发生结构或材料强度的显著增加。小鼠股骨骨折愈合遵循典型的软骨内骨化途径，小鼠骨折桥接的发生比大鼠快约1周。该骨折模型适用于使用不同近交系、转基因和敲除品系的小鼠进行骨折愈合的分子和遗传分析。
Objectives: The goal of this Study was to develop and characterize a closed femur fracture model for mice that can be used for the molecular and genetic analysis of fracture healing.Study Design: Longitudinal time study of species-specific fracture healing.Methods: A protocol was developed for creating reproducible, closed femur fractures in mice. Impending fractures were stabilized by retrograde insertion of a 0.01-inch-diameter, stainless steel wire into the intramedullary canal. The intramedullary wire was held in place with a wedge made from the first 2 mm of a 30-gauge needle. Fractures were produced by 3-point bending. Fracture healing was assessed by radiography.. histology, and torsional mechanical testing.Results: The mouse femur fracture technique produced good results with minimal loss of animals. Of the 246 mice used in the study, 22 mice were excluded due to poor fracture quality (8), loss of fracture stabilization (6), or to anesthesia death (8). Radiography showed a consistent pattern of fracture healing between mice with peak fracture callus volume evident at 10 (15 mice) to 14 days (18 mice) after fracture. Fracture bridging was apparent in all 3-week postfracture radiographs (35 mice). Histologic examination of 117 specimens at 9 time points showed chondrocyte differentiation within the fracture callus by 7 days after fracture, endochondral ossification occurring by 10 days after fracture, and bone remodeling evident as early as 3 weeks after fracture. Despite radiologic and histologic evidence of fracture bridging after 3 weeks, torsional mechanical testing of 68 mice at 3, 4, 6, and 12 weeks after fracture (group size of 15 to 18 in ice at each time point) indicated that significant increases in structural or material strength did not occur until 6 to 12 weeks after fracture.Conclusions: Femur fracture healing in mice follows a typical endochondral ossification pathway with fracture bridging occurring approximately 1 week faster in mice than rats. This fracture model is amenable to the molecular and genetic analysis of fracture healing using different inbred, transgenic, and knockout strains of mice.