Nuclear factor of activated T cells mediates fluid shear stress- and tensile strain-induced Cox2 in human and murine bone cells.
Nuclear factor of activated T cells mediates fluid shear stress- and tensile strain-induced Cox2 in human and murine bone cells.
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DOI：
10.1016/j.bone.2009.08.061
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发表时间：
2010-01
期刊：
影响因子：
4.1
通讯作者：
Lee, Francis Young-In
中科院分区：
文献类型：
--
作者：
Aydemir, Ayse B. Celil;Minematsu, Hiroshi;Gardner, Thomas R.;Kim, Kyung Ok;Ahn, Jae Mok;Lee, Francis Young-In
诸如间质流体剪切应力和拉伸应变的机械负荷刺激骨细胞，骨细胞通过改变骨量和结构来响应，以维持最佳的骨骼结构。骨细胞也适应骨植入物和改变的机械负荷。宿主骨与种植体之间的骨结合是种植体稳定性的前提。由于行走和其他日常活动期间的机械负荷，骨细胞和植入物之间会发生波动的流体压力和界面应变。在这项研究中，我们研究了机械刺激激活人类和小鼠骨细胞中一种新型转录因子的信号机制。活化T细胞核因子（NFAT）是在Ca++/钙调神经磷酸酶（Ca++/Cn）网络下游起作用的转录因子之一：Ca++/Cn网络是众所周知的炎症途径。在这项研究中，我们假设NFAT 2被激活，在响应机械刺激和介导Cox 2的表达。流体剪切应力和张应变导致成骨细胞系细胞中NFAT的核转位。发现Cn/NFAT轴的肽抑制剂阻断机械刺激介导的Cox 2诱导。此外，染色质免疫沉淀分析显示NFAT 2和人Cox 2启动子区之间的直接相互作用。此外，发现CnAβ敲除颅骨骨细胞对机械刺激的敏感性低于对照骨细胞。我们的研究为NFAT在骨细胞中细胞因子基因诱导的骨机械传导中的新作用提供了新的证据。
Mechanical loading such as interstitial fluid shear stress and tensile strain stimulates bone cells, which respond by changing bone mass and structure to maintain optimal skeletal architecture. Bone cells also adapt to bone implants and altered mechanical loading. Osseous integration between host bone and implants is a prerequisite for the stability of implants. Fluctuating fluid pressure and interfacial strains occur between bone cells and implants due to mechanical loading during walking and other daily activities. In this study, we examined the signaling mechanism by which mechanical stimulation activates a novel transcription factor in human and mouse bone cells. Nuclear factor of activated T cells (NFAT) is one of the transcription factors that act downstream of the Ca++/Calcineurin (Ca++/Cn) network: a well-known pathway of inflammation. In this study, we hypothesized that NFAT2 is activated in response to mechanical stimulation and mediates Cox2 expression. Fluid shear stress and tensile strain results in nuclear translocation of NFAT in cells of the osteoblastic lineage. A peptide inhibitor of the Cn/NFAT axis was found to block the mechanical stimulation-mediated Cox2 induction. Further, chromatin immunoprecipitation assay shows direct interaction between NFAT2 and the human Cox2 promoter region. Additionally, CnAβ knockout calvarial bone cells were found to be less sensitive than control bone cells to mechanical stimulation. Our study provides new evidence for a novel role for NFAT in bone mechanotransduction in the context of cytokine gene induction in bone cells.
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DOI：
10.1073/pnas.072647999
发表时间：
2002-04-02
影响因子：
11.1
作者：
Bueno, OF;Wilkins, BJ;Molkentin, JD
通讯作者：
Molkentin, JD
DOI：
10.1196/annals.1341.008
发表时间：
2005-01-01
期刊：
COMMUNICATIVE CARDIAC CELL
影响因子：
--
作者：
Bers, DM;Guo, T
通讯作者：
Guo, T
影响因子：
3.3
作者：
Cherian, PP;Siller-Jackson, AJ;Jiang, JX
通讯作者：
Jiang, JX
影响因子：
16
作者：
Aramburu, J;Garcia-Cozar, F;Hogan, PG
通讯作者：
Hogan, PG
影响因子：
15.9
作者：
Aliprantis, Antonios O.;Ueki, Yasuyoshi;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.