Deschner James, Hofman Cynthia R, Piesco Nicholas P, Agarwal Sudha
Department of Oral Medicine and Pathology, University of Pittsburgh School of Dental Medicine, Pittsburgh, Philadelphia 15261-1964, USA.
Curr Opin Clin Nutr Metab Care. 2003 May;6(3):289-93. doi: 10.1097/01.mco.0000068964.34812.2b.
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.
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.
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.
运动和被动活动对发炎关节具有修复作用，而在骨关节炎中观察到，过度的机械力会引发软骨破坏。然而，将机械信号转化为导致软骨破坏和修复的生化事件的细胞内机制仍存在矛盾之处。本综述总结了机械应力产生的信号如何引发软骨的修复或破坏。
低强度机械应变通过抑制白细胞介素-1β和肿瘤坏死因子-α诱导的参与软骨降解的多种促炎介质转录来抑制炎症。这还导致蛋白聚糖和胶原蛋白合成上调，而在发炎关节中这些合成被显著抑制。相反，高强度机械应变具有促炎作用，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-κB作为转录抑制/激活促炎基因以控制软骨细胞分解代谢过程的共同途径。低强度机械应变可阻止核因子-κB的核转位，从而抑制促炎基因表达，而高强度机械应变则诱导核因子-κB的反式激活，进而诱导促炎基因表达。
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-κB抑制的结果还是通过不同的合成代谢途径介导，尚待阐明。
