The effects of cyclic mechanical strain and tumor necrosis factor alpha on the response of cells of the meniscus
The effects of cyclic mechanical strain and tumor necrosis factor alpha on the response of cells of the meniscus
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DOI：
10.1016/j.joca.2004.08.007
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发表时间：
2004-12-01
影响因子：
7
通讯作者：
Guilak, F
中科院分区：
文献类型：
--
作者：
Fermor, B;Jeffcoat, D;Guilak, F
目的：膝关节半月板的细胞对它们的生物化学和生物力学环境的变化作出反应，改变基质成分和炎症介质的生物合成。肿瘤坏死因子α（TNF-α）是一种促炎细胞因子，参与骨关节炎和类风湿性关节炎的发病机制，但其对关节生理学或机械生物学的影响尚未完全了解。本研究的目的是研究的假设，周期性机械应变的aprocal细胞调节基质大分子和促炎介质的生物合成，并确定这种反应是否被改变由TNF-α。方法：细胞被分离从内三分之二的猪内侧aproci和进行双轴拉伸应变的5-15%，在0.5 Hz的频率。蛋白多糖，蛋白质，一氧化氮（NO），和前列腺素E-2的合成determined.Results：循环拉伸应变增加了一氧化氮的生产，通过上调一氧化氮合酶2（NOS 2），也增加了前列腺素E-2，蛋白多糖，和总蛋白的合成速率的方式，依赖于应变幅度。TNF-α增加NO和总蛋白的产生，但抑制蛋白多糖的合成速率。结论：促炎细胞因子可调节半月板细胞对机械信号的反应，提示生物力学和炎症因素均可能参与半月板负荷改变导致的关节疾病的进展。(C)2004年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objectives: Cells of the knee meniscus respond to changes in their biochemical and biomechanical environments with alterations in the biosynthesis of matrix constituents and inflammatory mediators. Tumor necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine that is involved in the pathogenesis of both osteoarthritis and rheumatoid arthritis, but its influence on meniscal physiology or mechanobiology is not fully understood. The objectives of this study were to examine the hypothesis that cyclic mechanical strain of meniscal cells modulates the biosynthesis of matrix macromolecules and pro-inflammatory mediators, and to determine if this response is altered by TNF-alpha.Methods: Cells were isolated from the inner two-thirds of porcine medial menisci and subjected to biaxial tensile strain of 5-15% at a frequency of 0.5 Hz. The synthesis of proteoglycan, protein, nitric oxide (NO), and prostaglandin E-2 were determined.Results: Cyclic tensile strain increased the production of nitric oxide through the upregulation of nitric oxide synthase 2 (NOS2) and also increased synthesis rates of prostaglandin E-2, proteoglycan, and total protein in a manner that depended on strain magnitude. TNF-alpha increased the production of NO and total protein, but inhibited proteoglycan synthesis rates. TNF-a prevented the mechanical stimulation of proteoglycan synthesis, and this effect was not dependent on NOS2.Conclusions: These findings indicate that pro-inflammatory cytokines can modulate the responses of meniscal cells to mechanical signals, suggesting that both biomechanical and inflammatory factors could contribute to the progression of joint disease as a consequence of altered loading of the meniscus. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.