MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells
MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells
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DOI：
10.1016/s0898-6568(02)00008-6
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发表时间：
2002-08-01
影响因子：
4.8
通讯作者：
Lafage-Proust, MH
中科院分区：
文献类型：
--
作者：
Granet, C;Vico, AGL;Lafage-Proust, MH
活化蛋白-1（AP-1）复合物在骨生理学中起关键作用，包括其对应变的响应。我们在成骨细胞ROS 17/2.8细胞中研究了基底变形（Flexcell）或刺激微重力（Clinostat）后7个AP-1成员的基因表达和核转位动力学。所有AP-1成员的基因表达和核转位诱导，在这两种条件下，其动力学的差异，除了在Clinostat中的fosB mRNA。下调蛋白激酶C（PKC）和COX 1/2或抑制ERK 1/2、p38（MAPK）或src激酶对Flexcell中AP-1 mRNA表达无明显影响。与此相反，ERK 1/2、p38（MAPK）和si-c激酶处理阻断了两种模型中几乎所有AP-1成员的核转位，除了变形后的Fra-1、JunD和旋转后的Fra-1、JunB。因此，在成骨细胞的机械环境的变化引起了显着的诱导大多数AP-1成员具有特定的动力学和MAPK和src激酶途径，这不同的细胞是否被拉伸或clinorated。(C)2002年爱思唯尔科学公司All rights reserved.
The activating protein-1 (AP-1) complex plays a critical role in bone physiology, including its response to strain. We Studied gene expression and nuclear translocation kinetics of the seven AP-1 members, after substrate deformation (Flexcell) or stimulated microgravity (Clinostat), in osteoblastic ROS17/2.8 cells. Gene expression and nuclear translocation of all the AP-1 members were induced, under both conditions, with differences in their kinetics, except fosB mRNA in the Clinostat. Downregulation of protein kinase C (PKC) and COX1/2 or inhibition of ERK1/2, p38(MAPK) or src kinases had no major effect oil AP-1 mRNA expression in the Flexcell. In contrast, ERK1/2, p38(MAPK) and si-c kinases treatment blocked nuclear translocation of almost all the AP-1 members in both models, except Fra-1, JunD after deformation and Fra-1, JunB after clinorotation. Thus, changes in the osteoblastic mechanical environment induced a dramatic induction of most of the AP-1 members with specific kinetics and involved MAPK and src kinase pathways, which differed whether the cells were stretched or clinorotated. (C) 2002 Elsevier Science Inc. All rights reserved.