Paracrine activation of extracellular signal-regulated kinase in a simple in vitro model of wounded osteoblasts.
Paracrine activation of extracellular signal-regulated kinase in a simple in vitro model of wounded osteoblasts.
复制标题
在受伤成骨细胞的简单体外模型中细胞外信号调节激酶的旁分泌激活。
DOI：
10.1016/s8756-3282(02)00824-4
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发表时间：
2002
期刊：
影响因子：
4.1
通讯作者：
Landesberg,R
中科院分区：
文献类型：
--
作者：
Katz,RW;Teng,SY;Thomas,S;Landesberg,R
成骨细胞对急性创伤的直接信号转导反应的特征不明显。我们已经开发了一个简单的成骨细胞创伤的体外模型，以研究骨创伤愈合的分子机制。在这里，我们报告的具体，快速，和瞬时磷酸化的细胞外信号调节激酶（ERK）1和2成骨细胞作为一个响应破坏（“创伤”）的融合单层。p38和应激活化蛋白激酶/c-jun N-末端激酶（SAPK/JNK）的丝裂原活化蛋白激酶（MAPK）级联未被这种扰动激活。对创伤的反应相当于通过加入外源性生长因子激活ERK，并且ERK的扰动依赖性磷酸化可以被肝素结合生长因子的抑制剂抑制。来自损伤单层的条件培养基可以诱导未扰动单层中ERK的磷酸化。使用免疫组织化学，它表明，磷酸化ERK水平增加的细胞不局限于伤口边缘。这些结果表明，ERK激活是成骨细胞对创伤的自分泌/旁分泌反应的结果。我们推测成骨细胞对创伤的反应是释放可溶性因子，这是骨创伤愈合过程中自分泌/旁分泌调节的一部分。
The immediate signal-transduction response of osteoblasts to acute trauma is poorly characterized. We have developed a simple in vitro model for osteoblast trauma to investigate aspects of the molecular mechanisms of wound healing in bone. Herein we report the specific, rapid, and transient phosphorylation of extracellular signal-regulated kinase (ERK) 1 and 2 in osteoblasts as a response to disruption (“wounding”) of a confluent monolayer. The mitogen-activated protein kinase (MAPK) cascades of p38 and stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) were not activated by this perturbation. The response to wounding was equivalent to the activation of ERK by the addition of exogenous growth factors, and the perturbation-dependent phosphorylation of ERK can be suppressed by an inhibitor of heparin-binding growth factors. Conditioned media from wounded monolayers can induce the phosphorylation of ERK in unperturbed monolayers. Using immunohistochemistry, it was demonstrated that the cells with increased levels of phosphorylated ERK were not localized to the wound edges. These results indicate that ERK activation is the result of an autocrine/paracrine response by osteoblasts to trauma. We speculate that osteoblasts respond to trauma with the release of soluble factors as part of an autocrine/paracrine modulation of the wound-healing process in bone.