Division of Orthopaedics, Shriners Hospital for Children, Montréal, QC, Canada.
Clin Orthop Relat Res. 2009 Dec;467(12):3190-8. doi: 10.1007/s11999-009-1065-6.
Previous reports suggest the application of exogenous BMPs can accelerate bone formation during distraction osteogenesis (DO). However, there are drawbacks associated with the use of exogenous BMPs. A possible alternative to the use of exogenous BMPs is to upregulate the expression of endogenous BMPs. Since DO results in spontaneously generated de novo bone formation in a uniform radiographic, histological, and biomechanical temporal sequence, a genetically engineered model lacking endogenous BMP2 should have measurable deficits in bone formation at different time points. We performed DO on BMP2(fl/+) and BMP2(fl/+ cre) mice using a miniature Ilizarov fixator. Distracted samples were collected at various time points and analyzed using real time-quantitative PCR, lCT, radiology, immunohistochemistry, histology, and biomechanical testing. Immunohistochemical studies of 34-day heterozygous samples showed reduced expression of BMP2, BMP7, BMPR1a, ACTR1, and ACTR2b. lCT analysis of 51-day heterozygous samples revealed a decrease in trabecular number and increase in trabecular separation. Biomechanical testing of 51-day heterozygous samples revealed decreased stiffness and increased ultimate displacement. Radiological analysis showed the heterozygotes contained a decreased bone fill score at 17, 34, and 51 days. These data suggest endogenous BMPs are important for bone healing and manipulating endogenous BMPs may help accelerate bone consolidation during DO.
先前的报告表明，外源性 BMP 的应用可以加速牵张成骨过程中的骨形成。然而，外源性 BMP 的使用存在一些缺点。一种替代外源性 BMP 的方法是上调内源性 BMP 的表达。由于牵张成骨导致新骨在统一的影像学、组织学和生物力学时间序列中自发形成，因此缺乏内源性 BMP2 的基因工程模型在不同时间点的骨形成中应该有可测量的缺陷。我们使用微型伊利扎罗夫固定器对 BMP2(fl/+)和 BMP2(fl/+ cre)小鼠进行了牵张成骨。在不同时间点采集牵张样本，并通过实时定量 PCR、lCT、放射学、免疫组织化学、组织学和生物力学测试进行分析。34 天杂合子样本的免疫组织化学研究显示 BMP2、BMP7、BMPR1a、ACTR1 和 ACTR2b 的表达减少。51 天杂合子样本的 lCT 分析显示，小梁数量减少，小梁分离增加。51 天杂合子样本的生物力学测试显示，刚度降低，最终位移增加。放射学分析显示，杂种在 17、34 和 51 天时的骨填充评分降低。这些数据表明内源性 BMP 对骨愈合很重要，而操纵内源性 BMP 可能有助于加速牵张成骨过程中的骨整合。
