EFFECTS OF NITRIC-OXIDE ON CHONDROCYTE MIGRATION, ADHESION, AND CYTOSKELETAL ASSEMBLY

Objective. The migration of cells of chondrocyte lineage is believed t o play a role in cartilage growth and repair, The present study examin ed 1) whether chondrocytes are capable of migration in vitro; and 2) t he effects of nitric oxide (NO) on chondrocyte migration, adhesion, an d cytoskeletal assembly. Methods. Chondrocyte migration was evaluated by 2 assays: 1) ''centrifugal'' migration within a 3-dimensional colla gen matrix (dot culture); and 2) directed migration under agarose in r esponse to bone morphogenetic protein, To assess the effects of NO, ch ondrocytes were treated with either exogenous NO (S-nitrosoglutathione [SNO-GSH]) or a mixture of cytokines known to induce endogenous NO pr oduction, The effects of NO on chondrocyte adhesion to fibronectin-coa ted surfaces, as well as on actin polymerization (determined by indire ct immunofluorescence), were also examined. Results. The capacity of c hondrocytes to migrate was demonstrated both by the dot culture and by agarose methods, Both SNO-GSH and endogenous NO induced by cytokines inhibited this migration, Exposure to NO also inhibited attachment of chondrocytes to fibronectin and disrupted assembly of actin filaments, These effects of SNO-GSH and cytokine-induced NO production were reve rsed in the presence of hemoglobin and the NO synthase inhibitor N-G-m onomethyl arginine, respectively. Conclusion. NO interferes with chond rocyte migration and attachment to fibronectin, an extracellular matri x protein, probably via effects on the actin cytoskeleton, These effec ts of NO may result in impairment of cartilage repair, by interfering with the extracellular matrix regulation of chondrocyte function.