Transforming Growth Factor β1 Regulates Tissue Inhibitor of Metalloproteinases—1 Expression in Differentiated Human Articular Chondrocytes

Abstract

Objective. To investigate the role of interleukin‐6 (IL‐6) and transforming growth factor β1 (TGF β1) in the regulation of tissue inhibitor of metalloproteinases—1 (TIMP‐1) synthesis in human articular chondrocytes.Methods. Articular cartilage was obtained from human knee joints 24 hours after death. Chondrocytes were isolated by collagenase digestion and embedded in low‐gelling‐temperature agarose. After stimulation by cytokines, total RNA was isolated and analyzed by Northern blotting. TIMP‐1 protein levels were determined using a competitive enzyme‐linked immunosorbent assay.Results. Human chondrocytes in agarose culture expressed messenger RNA (mRNA) for the IL‐6 receptor (gp80) and its signal‐transducing subunit gp130. In contrast to the findings in a previous study, IL‐6 did not stimulate TIMP‐1 expression in these cells, whereas TGF β1 was an important inducer of TIMP‐1 mRNA and protein synthesis.Conclusion. Our findings suggest that TGF β1 has a protective effect on the extracellular matrix of human articular chondrocytes.