TRANSFORMING GROWTH-FACTOR-BETA-1 REGULATES TISSUE INHIBITOR OF METALLOPROTEINASES-1 EXPRESSION IN DIFFERENTIATED HUMAN ARTICULAR CHONDROCYTES

Objective. To investigate the role of interleukin-6 (IL-6) and transfo rming growth factor beta 1 (TGF beta 1) in the regulation of tissue in hibitor of metalloproteinases-1 (TIMP-1) synthesis in human articular chondrocytes. Methods. Articular cartilage was obtained from human kne e joints 24 hours after death. Chondrocytes were isolated by collagena se digestion and embedded in low-gelling-temperature agarose. After st imulation by cytokines, total RNA was isolated and analyzed by Norther n blotting. TIMP-1 protein levels were determined using a competitive enzyme-linked immunosorbent assay. Results. Human chondrocytes in agar ose culture expressed messenger RNA (mRNA) for the IL-6 receptor (gp80 ) and its signal-transducing subunit gp130. In contrast to the finding s in a previous study, IL-6 did not stimulate TIMP-1 expression in the se cells, whereas TGF beta 1 was an important inducer of TIMP-1 mRNA a nd protein synthesis. Conclusion. Our findings suggest that TGF beta 1 has a protective effect on the extracellular matrix of human articula r chondrocytes.