Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures
Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures
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DOI：
10.1002/jor.20182
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发表时间：
2006-07-01
影响因子：
2.8
通讯作者：
Reddi, A. Hari
中科院分区：
文献类型：
--
作者：
Niikura, Takahiro;Hak, David J.;Reddi, A. Hari
骨不连是一个具有挑战性的问题，可能发生在某些骨折后。然而，对骨不连的分子基础研究甚少。骨形态发生蛋白（BMPs）在成骨过程中起着重要作用。然而，对于BMPs在导致骨不连形成的异常愈合中的表达模式知之甚少。这些事实促使我们使用大鼠实验模型研究并比较bmp及其拮抗剂在标准愈合骨折和骨不连中的基因表达模式。在大鼠股骨中建立了标准的闭合性愈合骨折和骨折部位骨膜烧灼产生的实验性萎缩性不连。在骨折后第3、7、10、14、21和28天，从标准愈合骨折的骨痂和不愈合的纤维组织中提取总RNA（每个时间点和每组n = 4）。通过基因芯片（Genechip(k) microarray）和实时定量RTPCR等方法研究BMP、BMP拮抗剂和其他调控分子的基因表达。BMP-2、3、3B、4、67、GDF-5、7和BMP拮抗剂noggin、drm、screlostin和BAMBI的基因表达在几个时间点上与标准愈合骨折相比，不愈合患者的基因表达明显降低。成骨bmp表达下调可能是骨折不愈合的原因。bmp与其内源性拮抗剂之间的平衡对于最佳骨折愈合至关重要。(c) 2006年骨科研究学会。Wiley期刊公司出版。
Nonunion is a challenging problem that may occur following certain bone fractures. However, there has been little investigation of the molecular basis of nonunions. Bone morphogenetic proteins (BMPs) play a significant role in osteogenesis. However, little is known about the expression patterns of BMPs in abnormal bone healing that results in nonunion formation. These facts prompted us to investigate and compare the gene expression patterns of BMPs and their antagonists in standard healing fractures and nonunions using rat experimental models. Standard closed healing fractures and experimental atrophic nonunions produced by periosteal cauterization at the fracture site were created in rat femurs. At postfracture days 3, 7, 10,14, 21, and 28, total RNA was extracted from the callus of standard healing fracture and fibrous tissue of nonunion (n. = 4 per each time point and each group). Gene expression of BMPs, BMP antagonists, and other regulatory molecules were studied by methods including Genechip(k) microarray and real -time quantitative RTPCR. Gene expression of BMP-2, 3, 3B, 4, 67 7, GDF-5, 7, and BMP antagonists noggin, drm, screlostin, and BAMBI were significantly lower in nonunions compared to standard healing fractures at several time points. Downregulation in expression of osteogenic BMPs may account for the nonunions of fracture. The balance between BMPs and their endogenous antagonists is critical for optimal fracture healing. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals,Inc.