EXPRESSION OF INTERLEUKIN-6 IN OSTEOARTHRITIC CHONDROCYTES AND EFFECTS OF FLUID-INDUCED SHEAR ON THIS EXPRESSION IN NORMAL HUMAN CHONDROCYTES IN-VITRO

This study tested the effect of fluid-induced shear on interleukin-6 e xpression in normal human articular chondrocytes in vitro. As determin ed by Northern blot analysis, interleukin-6 mRNA expression occurs in chondrocytes from osteoarthritic cartilage but not in normal chondrocy tes. Applying fluid-induced shear stress to primary high density cultu res of chondrocytes increased interleukin-6 mRNA signal 4-fold at 1 ho ur and 10 to 15-fold at 48 hours compared with unsheared control cultu res. At 48 hours, fluid-induced shear stress increased interleukin-6 p rotein levels in the culture medium 9 to 10-fold compared with unshear ed controls, mRNA signals for interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor-alpha in RNA from sheared or control chondr ocytes were not detected by Northern blotting. Transforming growth fac tor-beta mRNA signal was detectable but was not affected by shear. In contrast, human lung fibroblasts (WI-38) responded to fluid-induced sh ear with increased signal for transforming growth factor-beta, but not interleukin-6, mRNA. Both cell types did respond to interleukin-1 alp ha with increased interleukin-6 mRNA signal. These data demonstrate th at distortional forces, such as fluid-induced shear stress, alter inte rleukin-6 levels in normal chondrocytes in vitro and suggest that incr eased interleukin-6 expression in osteoarthritic cartilage may result, in part, from alterations in the mechanical loading of the tissue.