RHEUMATOID-ARTHRITIS SYNOVIAL FIBROBLAST AND U937 MACROPHAGE MONOCYTECELL-LINE INTERACTION IN CARTILAGE DEGRADATION/

Objective. To examine the interaction between synovial fibroblasts and macrophages in the context of cartilage degradation. Methods. An in v itro model of human cartilage degradation was used, in which purified populations of fibroblasts and macrophages were added to a radio-label ed cartilage disc, Cartilage destruction was measured by the percentag e of radiolabel release. Results. Fibroblasts, obtained from either rh eumatoid arthritis (RA) or osteoarthritis synovial tissue, could media te cartilage degradation if cocultured with the U937 macrophage cell l ine, Skin and RA bone marrow fibroblasts had no degradative effect on cartilage, Fibroblast-macrophage contact was not required for cartilag e degradation, Cartilage degradation by synovial fibroblasts was inhib ited by antibodies to tumor necrosis factor alpha (TNF alpha), interle ukin-1 beta (IL-1 beta), and IL-6, Cartilage degradation was almost co mpletely abrogated by a combination of antibodies to TNF alpha and IL- 1 beta, Contact between fibroblasts and cartilage was shown to be esse ntial, Antibodies to CD44, but not to intercellular adhesion molecule 1, markedly inhibited cartilage degradation. Conclusion. TNF alpha, IL -1 beta, and IL-6 were involved in the activation of synovial fibrobla sts to cause cartilage degradation, Cartilage degradation occurred onl y when fibroblasts were in contact with cartilage, CD44 was demonstrat ed to be involved in the fibroblast-cartilage interaction.