Alterations in gene expression in response to compression of nucleus pulposus cells.
Alterations in gene expression in response to compression of nucleus pulposus cells.
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DOI：
10.1016/j.spinee.2010.09.019
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Kang JD
中科院分区：
文献类型：
--
作者：
Sowa GA;Coelho JP;Bell KM;Zorn AS;Vo NV;Smolinski P;Niyonkuru C;Hartman R;Studer RK;Kang JD
很明显，机械力参与引发椎间盘退变，但也有可能发挥有益的作用。然而，由机械应力引发的信号通路和这些响应的阈值尚未阐明。我们已经开发了一种代谢活性压缩系统，其优点是能够在体外以及在其天然基质中测试细胞并控制暴露于环境因素。我们假设髓核细胞对压力有不同的分解代谢和合成代谢基因表达改变的阈值。本研究的目的是建立一种新型加压室的实用性，并检查不同幅度和持续时间的加压对髓核炎症、分解代谢和合成代谢基因表达的影响。椎间盘细胞对压力反应的体外对照检查。制造能够对髓核细胞施加0至20 MPa的流体静力学压缩的室。将健康兔髓核细胞在藻酸盐珠中培养，并暴露于0.7、2和4 MPa的静态压缩4或24小时。进行基因表达分析（实时聚合酶链反应），以比较对照和压缩细胞中的炎症标志物（诱导型一氧化氮合酶，环氧合酶-2），基质催化剂（基质金属蛋白酶-3）和抗代谢/合成代谢（金属蛋白酶组织抑制剂-1，aggrecan）。压缩导致基因表达的幅度和持续时间依赖性变化。增加幅度显示更多的抗代谢基因表达的变化，而持续时间的增加导致前代谢基因表达的增加。这些数据表明，有利的影响，压缩有关的基因参与基质稳态和前代谢基因表达的持续负荷水平的反应，符合创伤的影响。这些数据提供了对压缩如何影响细胞信号传导的更好理解，这有可能被利用来启动修复和防止基质分解。
It is clear that mechanical forces are involved in initiating disc degeneration but also have the potential to exert beneficial effects. However, the signaling pathways initiated by mechanical stress and thresholds for these responses have not been elucidated. We have developed a metabolically active compression system with the advantages of having the ability to test cells in vitro as well as within their native matrix and control exposure to environmental factors. We hypothesized that nucleus pulposus cells would respond to compressive stress with different thresholds for alterations in catabolic and anabolic gene expression. The purpose of the study was to establish the utility of a novel compression chamber and examine the effects of various magnitudes and durations of compression on nucleus pulposus inflammatory, catabolic, and anabolic gene expression. In vitro controlled examination of intervertebral disc cell responses to compression. A chamber capable of imparting 0 to 20 MPa of hydrostatic compression onto nucleus pulposus cells was fabricated. Healthy rabbit nucleus pulposus cells were cultured in alginate beads and exposed to static compression at 0.7, 2, and 4 MPa for 4 or 24 hours. Gene expression analysis (real-time polymerase chain reaction) was performed to compare markers of inflammation (inducible nitric oxide synthase, cyclooxygenase-2), matrix catabolism (matrix metalloproteinase-3), and antica-tabolic/anabolic metabolism (tissue inhibitor of metalloproteinase-1, aggrecan) in control and compressed cells. Compression resulted in magnitude- and duration-dependent changes in gene expression. Increasing magnitudes showed more anticatabolic gene expression changes, whereas increasing duration resulted in increases in procatabolic gene expression. These data demonstrate favorable effects of compression in relation to genes involved in matrix homeostasis and procatabolic gene expression in response to sustained loading levels, consistent with traumatic effects. These data provide an improved understanding of how compression affects cell signaling, which has the potential to be exploited to initiate repair and prevent matrix breakdown.
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影响因子：
3
作者：
Handa, T;Ishihara, H;Obata, K
通讯作者：
Obata, K
影响因子：
7.3
作者：
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通讯作者：
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DOI：
10.1016/s1529-9430(03)00174-8
发表时间：
2004-01-01
期刊：
The spine journal : official journal of the North American Spine Society
影响因子：
--
作者：
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通讯作者：
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影响因子：
2.8
作者：
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通讯作者：
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影响因子：
2.8
作者：
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