Abstract
BackgroundTenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. We analyzed TN-C expression in normal and osteoarthritic (OA) human cartilage, and evaluated its capacity to induce inflammatory and catabolic mediators in chondrocytes in vitro. The effect of TN-C on proteoglycan loss from articular cartilage in culture was also assessed.MethodsTN-C in culture media, cartilage extracts, and synovial fluid of human and animal joints was quantified using a sandwich ELISA and/or analyzed by Western immunoblotting. mRNA expression of TN-C and aggrecanases were analyzed by Taqman assays. Human and bovine primary chondrocytes and/or explant culture systems were utilized to study TN-C induced inflammatory or catabolic mediators and proteoglycan loss. Total proteoglycan and aggrecanase -generated ARG-aggrecan fragments were quantified in human and rat synovial fluids by ELISA.ResultsTN-C protein and mRNA expression were significantly upregulated in OA cartilage with a concomitant elevation of TN-C levels in the synovial fluid of OA patients. IL-1 enhanced TN-C expression in articular cartilage. Addition of TN-C induced IL-6, PGE2, and nitrate release and upregulated ADAMTS4 mRNA in cultured primary human and bovine chondrocytes. TN-C treatment resulted in an increased loss of proteoglycan from cartilage explants in culture. A correlation was observed between TN-C and aggrecanase generated ARG-aggrecan fragment levels in the synovial fluid of human OA joints and in the lavage of rat joints that underwent surgical induction of OA.ConclusionsTN-C expression in the knee cartilage and TN-C levels measured in the synovial fluid are significantly enhanced in OA patients. Our findings suggest that the elevated levels of TN-C could induce inflammatory mediators and promote matrix degradation in OA joints.
Highlights
Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes
We have demonstrated a novel role for increased TN-C levels in the OA joint in promoting proteoglycan loss in addition to mediating inflammatory signals, which is supported by a correlation between TN-C levels in the knee synovial fluid and proteoglycan loss from the articular cartilage in human and rat joints
The factors regulating the expression of TN-C are IL-1b [31], tumor necrosis factor-a (TNFa) [31], transforming growth factor-b (TGFb) [32], and basic fibroblast growth factor [33], all of which are present at increased levels in the joints of patients with OA compared with those of normal patients [34]
Summary
Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. Tenascin-C (TN-C) is a modular, multifunctional extracellular matrix (ECM) glycoprotein that is associated with tissue injury and repair. It was discovered originally in gliomas, muscle tissue and in the nervous system, and called by different names: myotendinous antigen, glial/mesenchymal ECM protein, cytotactin, J1 220/200, neuronectin and hexabrachion [1]. It was later found in the osteotendinous junction and superficial layers of articular cartilage [2,3]. A correlation between TN-C levels in synovial fluid and degree of cartilage degradation [14] or radiographic progression of knee OA [15] has been shown
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