TSG‐6 expression in human articular chondrocytes: Possible implications in joint inflammation and cartilage degradation

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Abstract
Objective. The hyaluronan‐binding protein TSG‐6 (tumor necrosis factor‐stimulated gene 6) forms a stable complex with the serine protease inhibitor, inter‐α‐inhibitor, potentiates the inhibition of plasmin activity, and has antiinflammatory effects in vivo. This study examines the expression of TSG‐6 in human articular chondrocytes and cartilage. Methods. Human articular chondrocytes and cartilage explants were stimulated with cytokines, growth factors, and other agents. TSG‐6 expression was analyzed by imaging‐assisted Northern and Western blotting. Results. TSG‐6 messenger RNA (mRNA) expression was upregulated by cytokines and growth factors, predominantly interleukin‐1β (IL‐1β), tumor necrosis factor α (TNFα), platelet‐derived growth factor AA (PDGF‐AA), and transforming growth factor β1 (TGFβ1). TSG‐6 mRNA induction by TGFβ1 was delayed as compared with IL‐1β. Treatment of the cells with the glucocorticoid dexamethasone neither induced TSG‐6 mRNA nor did it affect IL‐1β‐induced transcript levels. TSG‐6 mRNA induction may involve several signal transduction pathways. The strong transcriptional stimulation by phorbol myristate acetate suggests protein kinase C (PKC)‐mediated signaling. In contrast, PKA‐ and Cadependent signals are only marginally involved as messengers leading to increased TSG‐6 levels after IL‐1β and TNFα treatment. In chondrocyte and cartilage organ cultures, both free TSG‐6 (35 kd) and the complex with inter‐α‐inhibitor (120 kd) were present and upregulated by IL‐1β, TNFα, or TGFβ1. Conclusion. Chondrocytes are a source of TSG‐6 which may play a role in cartilage remodeling and joint inflammation.