Cyclic tensile strain acts as an antagonist of IL-1 beta actions in chondrocytes

Inflammatory cytokines play a major role in cartilage destruction in diseas es such as osteoarthritis and rheumatoid arthritis, Because physical therap ies such as continuous passive motion yield beneficial effects on inflamed joints, we examined the intracellular mechanisms of mechanical strain-media ted actions in chondrocytes. By simulating the effects of continuous passiv e motion with cyclic tensile strain (CTS) on chondrocytes in vitro, we show that CTS is a potent antagonist of IL-1 beta actions and acts as both an a nti-inflammatory and a reparative signal. Low magnitude CTS suppresses IL-1 beta-induced mRNA expression of multiple proteins involved in catabolic re sponses, such as inducible NO synthase, cyclo-oxygenase Ii, and collagenase . CTS also counteracts cartilage degradation by augmenting mRNA expression for tissue inhibitor of metalloproteases and collagen type II that are inhi bited by IL-1 beta, Additionally, CTS augments the reparative process via h yperinduction of aggrecan mRNA expression and abrogation of IL-1 beta-induc ed suppression of proteoglycan synthesis. Nonetheless, the presence of an i nflammatory signal is a prerequisite for the observed CTS actions, as expos ure of chondrocytes to CTS alone has little effect on these parameters. Fun ctional analysis suggests that CTS-mediated anti-inflammatory actions are n ot mediated by IL-1R down-regulation. Moreover, as an effective antagonist of IL-1 beta, the actions of CTS may involve disruption/regulation of signa l transduction cascade of IL-1 beta upstream of mRNA transcription. These o bservations are the first to show that CTS directly acts as an anti-inflamm atory signal on chondrocytes and provide a molecular basis for its actions.