Transforming growth factor β1, a major stimulator of hyaluronan synthesis in human synovial lining cells

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Abstract
Objective: To investigate the role of cytokines and growth factors in the regulation of hyaluronan synthesis in human synovial lining cells. Methods. Synovial lining cells were obtained from human knee joints, isolated by the explant method, and characterized by immunocytochemistry using monoclonal antibodies against monocyte/macrophage markers as well as antibodies against hyaluronan synthase. After stimulation by cytokines and growth factors, hyaluronan was measured by radiometric assay. The molecular weight distribution of the hyaluronan synthesized was determined by high-performance gelpermeation liquid chromatography. To test the effect of oxygen-derived free radicals, the concentration and molecular weight distribution of hyaluronan were determined in the presence and absence of catalase and superoxide dismutase. Results. Hyaluronan synthesis was stimulated in synovial lining cells by transforming growth factor β1 (TGFβ1), interleukin-1β (IL-1β), and to a lesser extent by tumor necrosis factor α (TNFα). Analysis of the molecular weight distribution of hyaluronan after stimulation of synovial lining cells with TGFβ1, IL-1β, and TNFα indicated that hyaluronan is synthesized in a high molecular weight form and might be degraded in the course of inflammatory processes by oxygen-derived free radicals. Conclusion. Our findings suggest that TGFβ1 is a major stimulator of hyaluronan synthesis in human synovial lining cells and might be involved in the pathogenic mechanisms of joint swelling in inflammatory and degenerative joint diseases.

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