内源性骨形态发生蛋白在正常骨骼修复中的作用。

The role of endogenous bone morphogenetic proteins in normal skeletal repair.

机构信息

Department of Orthopaedic Surgery, Boston University Medical Center, 715 Albany Street, R-205, Boston, MA 02118-2393, USA.

出版信息

Injury. 2009 Dec;40 Suppl 3:S4-7. doi: 10.1016/S0020-1383(09)70003-8.

Abstract

Bone morphogenetic proteins play a key role in the regulation of the three major phases of fracture healing; the inflammatory response, the chondrogenic stage and the osteogenic stage. BMP-2 and 4 show a rapid response during the initial inflammatory stage, and BMP-2 has been shown to be essential for fracture healing to occur. BMP-2 and 4 are also present in the chondrogenic stage, although expression levels of BMP-3b (GDF10) and BMP-6 seemingly have specific peaks at day 7, suggesting a crucial role in this process. BMP-3, 4 and 5 are also abundantly present during this stage. In the osteogenic stage studies have shown that BMPs 1, 2, 3, 3b, 4, 5, 6, 7 and 8A have high levels of expression. It is important to note that of these, BMP-3 and 4 have a peak in their expression and BMP-7 and 8A are almost exclusively expressed during day 14 and 21. The expression of the different BMPs in these stages is believed to be orchestrated by autoregulatory activation between the BMPs, negative feed back loops and external antagonists. Alterations of the BMP signaling pathway, either by direct targeting of the BMPs or by their inhibitors has been shown to interfere with embryologic skeletal development and a post natal regenerative repair following skeletal trauma.

摘要

骨形态发生蛋白在调节骨折愈合的三个主要阶段中起着关键作用;炎症反应、软骨生成阶段和成骨阶段。BMP-2 和 4 在初始炎症阶段表现出快速反应,并且 BMP-2 已被证明对于骨折愈合是必不可少的。BMP-2 和 4 也存在于软骨生成阶段,尽管 BMP-3b(GDF10)和 BMP-6 的表达水平在第 7 天似乎有特定的峰值,表明它们在这个过程中具有关键作用。BMP-3、4 和 5 在这个阶段也大量存在。在成骨阶段的研究表明,BMPs 1、2、3、3b、4、5、6、7 和 8A 表达水平较高。值得注意的是,其中 BMP-3 和 4 的表达水平达到峰值,BMP-7 和 8A 在第 14 天和第 21 天几乎仅表达。这些阶段中不同 BMP 的表达被认为是由 BMP 之间的自动调节激活、负反馈回路和外部拮抗剂协调的。BMP 信号通路的改变,无论是通过直接靶向 BMP 还是通过其抑制剂,都已被证明会干扰胚胎骨骼发育和骨骼创伤后的产后再生修复。

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