Reduced expression of BMP-3 due to mechanical loading -: A link between mechanical stimuli and tissue differentiation
Reduced expression of BMP-3 due to mechanical loading -: A link between mechanical stimuli and tissue differentiation
复制标题
DOI：
10.1080/000164700317362172
复制
发表时间：
2000-12-01
期刊：
影响因子：
--
通讯作者：
Vukicevic, S
中科院分区：
文献类型：
--
作者：
Aspenberg, P;Basic, N;Vukicevic, S
力学信号和BMP的表达似乎参与了骨折修复过程中控制软骨分化的过程，但力学和BMP信号之间的联系尚不清楚。在这项对大鼠的研究中，我们使用骨腔来观察BMP基因的表达是如何在诱导软骨形成的机械载荷机制中发生变化的。我们用归一化的逆转录聚合酶链式反应(RT-PCR)比较了同一大鼠在加载和未加载小室中仍未分化的组织中转化生长因子β-1、骨形态发生蛋白-2、3、4、5、6、7、CDMP-1、2和ALK-2和3的表达。所有标本均有转化生长因子-β1、骨形态发生蛋白-2和骨形态发生蛋白-4的表达，无骨形态发生蛋白5-7和CDMPs的表达。加载1周后，未加载的8只动物中有7只在对照标本中有骨形态发生蛋白-S的表达，而在对侧加载的动物中只有1只表达。加载2周后，BMP-3表达模式不明显，但两个时间组加在一起，仍有9只大鼠负载侧BMP-3表达减少，1只表达增多，5只表达无差异(p=0.01)。1周时ALK-2在所有表达BMP-3的标本中均有表达，其余标本均未见表达。术后2周，ALK-2在所有标本中均有表达。因此，在这个模型中，已知的诱导软骨形成的负荷机制导致BMP-3和ALK-2的下调。这一结果与BMP-3抑制分化的观点一致，就像最近所描述的那样。这一作用似乎与ALK-2受体有关。最重要的是，结果表明机械信号和BMP表达之间存在联系，因此Me诱导抑制BMP-3的下调能够促进软骨的诱导。
Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We com pared the still undifferentiated tissue in loaded and un loaded chambers in the same rat regarding the expression of TGF beta -1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGF beta -1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none, 1 week after loading started, BMP-S was strongly expressed in the un loaded control specimens in 7 of 8 animals, but detectable in only 1 of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 expression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more in 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 was expressed in all specimens. Thus, a loading regime, known to induce cartilage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recently described. This role appears to be linked to the ALK-2 receptor. Most importantly, the results indicate a link between mechanical signaling and BMP expression such that me chanically-induced down-regulation of the inhibiting BMP-3 enabled the induction of cartilage.