Expression of bone morphogenetic proteins during membranous bone healing
Expression of bone morphogenetic proteins during membranous bone healing
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DOI：
10.1097/00006534-200101000-00018
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发表时间：
2001-01-01
影响因子：
3.6
通讯作者：
Longaker, MT
中科院分区：
文献类型：
--
作者：
Spector, JA;Luchs, JS;Longaker, MT
tk:2对于重建整形外科医生来说，膜性骨折愈合的分子生物学知识变得越来越重要。了解膜性骨折修复过程中表现出的复杂基因表达模式对于设计治疗方法至关重要，这些治疗方法可以通过有策略地操纵正常的基因表达过程来增加骨折愈合或加速正常的骨修复。在本研究中，我们建立了大鼠膜性骨修复模型。该模型由于技术简单、可重复性和相对较低的成本而具有很大的实用性。此外，它是通过免疫定位和/或原位杂交技术分析膜性骨修复分子调控的有力工具。在本研究中，在下颌骨的尾侧进行截骨，从而产生稳定的骨缺损，无需外部或内部固定。28只Sprague-Dawley大鼠分别于术后1、2、3、4、5、6和8周处死，对其愈合过程进行组织学分类。此外，利用这种新模型，我们分析了在膜性骨愈合的背景下，骨形态发生蛋白（BMP）家族几个成员的时间和空间表达模式，这些成员已知是成骨细胞谱系的关键调节因子。我们的数据表明，BMP-2/-4和BMP-7，也被称为成骨蛋白-1 (OP-1)，在膜性骨折愈合的早期阶段由成骨细胞、破骨细胞和其他更原始的间充质细胞表达。这些蛋白在骨重塑过程中继续表达，尽管不那么明显。BMP-2/-4和OP-1免疫染色恢复到基线强度与成熟板层骨的组织学外观一致。综上所述，这些数据强调了骨形态发生蛋白在膜性骨修复过程中发挥的潜在重要调节作用。
tk:2For the reconstructive plastic surgeon, knowledge of the molecular biology underlying membranous fracture healing is becoming increasingly vital. Understanding the complex patterns of gene expression manifested during the course of membranous fracture repair will be crucial to designing therapies that augment poor fracture healing or that expedite normal osseous repair by strategic manipulation of the normal course of gene expression. Sn the current study, ive present a rat model of membranous bone repair. This model has great utility because of its technical simplicity, reproducibility, and relatively low cost. Furthermore, it is a powerful tool for analysis of the molecular regulation of membranous bone repair by immunolocalization and/or in situ hybridization techniques.In this study, an osteotomy was made within the caudal half of the hemimandible, thus producing a stable bone defect without the need for external or internal fixation. The healing process was then catalogued histologically in 28 Sprague-Dawley rats that were serially killed at 1, 2, 3, 4, 5, 6, and 8 weeks after operation. Furthermore, using this novel model, we analyzed, within the context of membranous bone healing, the temporal and spatial expression patterns of several members of the bone morphogenetic protein (BMP) family, known to be critical regulators of cells of osteoblast Lineage. Our data suggest that BMP-2/-4 and BMP-7, also known as osteogenic protein-1 (OP-1), are expressed by osteoblasts, osteoclasts, and other more primitive mesenchymal cells within the fracture callus during the early stages of membranous fracture healing. These proteins continue to be expressed during the process of bone remodeIing, albeit less prominently. The return of BMP-2/-4 and OP-1 immunostaining to baseline intensity coincides with the histological appearance of mature lamellar bone. Taken together, these data underscore the potentially important regulatory role played by the bone morphogenetic proteins in the process of membranous bone repair.