OBJECTIVE: To examine the interaction between synovial fibroblasts and macrophages in the context of cartilage degradation. METHODS: An in vitro model of human cartilage degradation was used, in which purified populations of fibroblasts and macrophages were added to a radiolabeled cartilage disc. Cartilage destruction was measured by the percentage of radiolabel release. RESULTS: Fibroblasts, obtained from either rheumatoid arthritis (RA) or osteoarthritis synovial tissue, could mediate cartilage degradation if cocultured with the U937 macrophage cell line. Skin and RA bone marrow fibroblasts had no degradative effect on cartilage. Fibroblast-macrophage contact was not required for cartilage degradation. Cartilage degradation by synovial fibroblasts was inhibited by antibodies to tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6. Cartilage degradation was almost completely abrogated by a combination of antibodies to TNF alpha and IL-1 beta. Contact between fibroblasts and cartilage was shown to be essential. 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 fibroblasts to cause cartilage degradation. Cartilage degradation occurred only when fibroblasts were in contact with cartilage. CD44 was demonstrated to be involved in the fibroblast-cartilage interaction.
OBJECTIVE: To examine the interaction between synovial fibroblasts and macrophages in the context of cartilage degradation. METHODS: An in vitro model of humancartilage degradation was used, in which purified populations of fibroblasts and macrophages were added to a radiolabeled cartilage disc. Cartilage destruction was measured by the percentage of radiolabel release. RESULTS: Fibroblasts, obtained from either rheumatoid arthritis (RA) or osteoarthritis synovial tissue, could mediate cartilage degradation if cocultured with the U937 macrophage cell line. Skin and RA bone marrow fibroblasts had no degradative effect on cartilage. Fibroblast-macrophage contact was not required for cartilage degradation. Cartilage degradation by synovial fibroblasts was inhibited by antibodies to tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6. Cartilage degradation was almost completely abrogated by a combination of antibodies to TNF alpha and IL-1 beta. Contact between fibroblasts and cartilage was shown to be essential. 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 fibroblasts to cause cartilage degradation. Cartilage degradation occurred only when fibroblasts were in contact with cartilage. CD44 was demonstrated to be involved in the fibroblast-cartilage interaction.
Authors: H Tsuboi; Y Matsui; K Hayashida; S Yamane; M Maeda-Tanimura; A Nampei; J Hashimoto; R Suzuki; H Yoshikawa; T Ochi Journal: Ann Rheum Dis Date: 2003-03 Impact factor: 19.103