Integrin-mediated mechanotransduction in IL-1β stimulated chondrocytes

Integrin-mediated mechanotransduction in IL-1β stimulated chondrocytes
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DOI:
10.1007/s10237-006-0032-3
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发表时间:
2006-06-01
影响因子:
3.5
通讯作者:
Lee, D. A.
Lee, D. A.
中科院分区:
工程技术2区
文献类型:
--
作者:
Chowdhury, T. T.;Appleby, R. N.;Lee, D. A.

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机械负荷和白细胞介素-1 β(IL-1 β)通过不同的信号机制影响关节软骨细胞释放一氧化氮(NO)和前列腺素E-2(PGE(2))。各自信号通路之间相互作用的确切性质仍不清楚。最近的研究表明,整合素作为机械感受器,可以将细胞外刺激转化为细胞内信号,从而影响细胞反应。目前的研究表明,应用动态压缩诱导的抑制NO和上调的细胞增殖和蛋白聚糖合成的存在和不存在的IL-1 β。在没有IL-1 β的情况下,PGE(2)的释放不受动态压缩的影响,但在细胞因子存在的情况下受到抑制。整合素结合肽GRGDSP消除或逆转了在存在和不存在IL-1 β的情况下评估的所有四个参数中的压缩诱导的改变。非结合对照肽GRADSP没有作用。这些数据清楚地表明,在存在和不存在IL-1 β的情况下,软骨细胞对动态压缩的代谢反应是整联蛋白介导的。
Mechanical loading and interleukin-1 beta (IL-1 beta) influence the release of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) from articular chondrocytes via distinct signalling mechanisms. The exact nature of the interplay between the respective signalling pathways remains unclear. Recent studies have shown that integrins act as mechanoreceptors and may transduce extracellular stimuli into intracellular signals, thereby influencing cellular response. The current study demonstrates that the application of dynamic compression induced an inhibition of NO and an upregulation of cell proliferation and proteoglycan synthesis in the presence and absence of IL-1 beta. PGE(2) release was not affected by dynamic compression in the absence of IL-1 beta but was inhibited in the presence of the cytokine. The integrin binding peptide, GRGDSP, abolished or reversed the compression-induced alterations in all four parameters assessed in the presence and absence of IL-1 beta. The non-binding control peptide, GRADSP, had no effect. These data clearly demonstrate that the metabolic response of the chondrocytes to dynamic compression in the presence and absence of IL-1 beta, are integrin mediated.