Cyclic tensile stress exerts antiinflammatory actions on chondrocytes by inhibiting inducible nitric oxide synthase

Continuous passive motion manifests therapeutic effects on inflamed articul ar joints by an as-yet-unknown mechanism. Here, we show that application of cyclic tensile stress (CTS) in vitro abrogates the catabolic effects of IL -1 beta on chondrocytes. The effects of CTS are mediated by down-regulation of IL-1 beta-dependent inducible NO production, and are directly attribute d to the inhibition of inducible NO synthase (iNOS) mRNA expression and pro tein synthesis. The inhibition of iNOS induction by CTS is paralleled by ab rogation of IL-1 beta-induced down-regulation of proteoglycan synthesis. Fu rthermore, CTS inhibits iNOS expression and up-regulates proteoglycan synth esis at concentrations of IL-1 beta frequently observed in inflamed arthrit ic joints, suggesting that the actions of CTS may be clinically relevant in suppressing the sustained effects of pathological levels of IL-1 beta in v ivo. These results are the first to demonstrate that mechanisms of the intr acellular actions of CTS in IL-1 beta-activated chondrocytes are mediated t hrough inhibition of a key molecule in the signal transduction pathway that leads to iNOS expression.