Signal transduction by mechanical strain in chondrocytes

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.