Signal transduction by mechanical strain in chondrocytes
Signal transduction by mechanical strain in chondrocytes
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DOI：
10.1097/01.mco.0000068964.34812.2b
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发表时间：
2003-05-01
影响因子：
3.1
通讯作者：
Agarwal, S
中科院分区：
文献类型：
--
作者：
Deschner, J;Hofman, CR;Agarwal, S
运动和被动运动对发炎的关节有修复作用，而在骨关节炎中观察到过度的机械力会导致软骨破坏。然而，将机械信号转化为负责软骨破坏和修复的生化事件的细胞内机制仍然是矛盾的。本文综述了由机械应力产生的信号如何启动软骨的修复或破坏。近期研究发现，低强度的机械应变通过抑制il -1 β和tnf α诱导的参与软骨降解的多种促炎介质的转录来抑制炎症。这也会导致蛋白聚糖和胶原蛋白合成的上调，在发炎的关节中被严重抑制。相反，高强度的机械应变是促炎的，在抑制基质合成的同时引发软骨破坏。研究表明，机械信号利用核因子κ B作为促炎基因转录抑制/激活的共同途径来控制软骨细胞的分解代谢过程。低强度机械应变阻止核因子kappa B的核易位，抑制促炎基因的表达，而高强度机械应变诱导核因子kappa B的反激活，从而诱导促炎基因的表达。生理水平的机械信号或运动的有益作用可能是由于它们能够抑制促炎/分解代谢介质的信号转导途径，同时刺激合成代谢途径。这些合成代谢信号是核因子κ B抑制的结果，还是通过不同的合成代谢途径介导的，目前尚不清楚。
Purpose of review Exercise and passive motion exert reparative effects on inflamed joints, whereas excessive mechanical forces initiate cartilage destruction as observed in osteoarthritis. However, the intracellular mechanisms that convert mechanical signals into biochemical events responsible for cartilage destruction and repair remain paradoxical. This review summarizes how signals generated by mechanical stress may initiate repair or destruction of cartilage.Recent findings Mechanical strain of low magnitude inhibits inflammation by suppressing IL-1beta and TNF-alpha-induced transcription of multiple proinflammatory mediators involved in cartilage degradation. This also results in the upregulation of proteoglycan and Collagen synthesis that is drastically inhibited in inflamed joints. On the contrary, mechanical strain of high magnitude is proinflammatory and initiates cartilage destruction while inhibiting matrix synthesis. Investigations reveal that mechanical signals exploit nuclear factor-kappa B as a common pathway for transcriptional inhibition/activation of proinflammatory genes to control catabolic processes in chondrocytes. Mechanical strain of low magnitude prevents nuclear translocation of nuclear factor kappa B, resulting in the suppression of proinflammatory gene expression, whereas mechanical strain of high magnitude induces transactivation of nuclear factor kappa B, and thus proinflammatory gene induction.Summary The beneficial effects of physiological levels of mechanical signals or exercise may be explained by their ability to suppress the signal transduction pathways of proinflammatory/catabolic mediators, while stimulating anabolic pathways. Whether these anabolic signals are a consequence of the inhibition of nuclear factor kappa B or are mediated via distinct anabolic pathways is yet to be elucidated.