Dynamic compression inhibits the synthesis of nitric oxide and PGE2 by IL-1β-stimulated chondrocytes cultured in agarose constructs

Both mechanical loading and interleukin-1 beta (IL-1 beta) are known to regulate metabolic processes in articular cartilage through pathways mediated by nitric oxide (NO.) and PGE(2). This study uses a well-characterized model system involving isolated chondrocytes cultured in agarose constructs to test the hypothesis that dynamic compression alters the synthesis of (NO)-N-. and PGE, by IL-1 beta -stimulated articular chondrocytes. The data presented demonstrate for the first time that dynamic compression counteracts the effects of IL-1 beta on articular chondrocytes by suppressing both (NO)-N-. and PGE, synthesis. Inhibitor experiments indicated that the dynamic compression-induced inhibition of PGE2 synthesis and stimulation of proteoglycan synthesis were (NO)-N-. mediated, while compression-induced stimulation of cell proliferation was (NO)-N-. independent. The inhibition of (NO)-N-. and PGE, by dynamic compression is a finding of major significance that could contribute to the development of novel strategies for the treatment of cartilage-degenerative disorders. (C) 2001 Academic Press.