A role for hedgehog signaling in the differentiation of the insertion site of the patellar tendon in the mouse.
A role for hedgehog signaling in the differentiation of the insertion site of the patellar tendon in the mouse.
复制标题
刺猬信号传导在小鼠the骨肌腱插入位点的分化中的作用。
DOI：
10.1371/journal.pone.0065411
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wylie C
中科院分区：
文献类型：
--
作者：
Liu CF;Breidenbach A;Aschbacher-Smith L;Butler D;Wylie C
肌腱通常由两个组织学上不同的区域组成：中间物质和插入部位。我们之前表明，刺猬蛋白（Hh）信号通路的下游效应子Gli1仅在小鼠髌腱分化过程中的插入位点表达。为了测试 Hh 信号传导的功能作用，我们使用 Cre/Lox 系统在体内靶向 Smoothened (Smo) 基因。中间物质中 Hh 途径的组成型激活导致插入位点的分子标记，例如II 型胶原蛋白，在中间物质中异位表达或上调。使用一种新颖的体外器官培养方法证实了这一点。相反，当巩膜阳性细胞群中的 Smo 被切除时，纤维软骨插入位点的发育受到影响。全转录组分析显示，插入位点中参与软骨形成和矿化的基因表达下调，并且插入位点标记的表达减少。对在缺乏 Hh 信号传导的情况下发育的成年小鼠髌腱进行的生物力学测试显示，尽管突变组的线性模量并不显着低于对照组，但肌腱的结构特性（较低的线性刚度和较大的位移）和材料特性（较大的应变）受到损害。这些研究为 Hh 信号在肌腱发育过程中的作用提供了新的见解。
Tendons are typically composed of two histologically different regions: the midsubstance and insertion site. We previously showed that Gli1, a downstream effector of the hedgehog (Hh) signaling pathway, is expressed only in the insertion site of the mouse patellar tendon during its differentiation. To test for a functional role of Hh signaling, we targeted the Smoothened (Smo) gene in vivo using a Cre/Lox system. Constitutive activation of the Hh pathway in the mid-substance caused molecular markers of the insertion site, e.g. type II collagen, to be ectopically expressed or up-regulated in the midsubstance. This was confirmed using a novel organ culture method in vitro. Conversely, when Smo was excised in the scleraxis-positive cell population, the development of the fibrocartilaginous insertion site was affected. Whole transcriptome analysis revealed that the expression of genes involved in chondrogenesis and mineralization was down-regulated in the insertion site, and expression of insertion site markers was decreased. Biomechanical testing of murine adult patellar tendon, which developed in the absence of Hh signaling, showed impairment of tendon structural properties (lower linear stiffness and greater displacement) and material properties (greater strain), although the linear modulus of the mutant group was not significantly lower than controls. These studies provide new insights into the role of Hh signaling during tendon development.
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DOI：
10.1016/j.biocel.2004.01.007
发表时间：
2004-06-01
影响因子：
4
作者：
Chiquet-Ehrismann, R;Tucker, RP
通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
Wylie C
影响因子：
3.7
作者：
Gu Y;Runyan C;Shoemaker A;Surani MA;Wylie C
通讯作者：
Wylie C