Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage

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.

The Role of Changes in Extracellular Matrix of Cartilage in the Presence of Inflammation on the Pathology of Osteoarthritis

“…Elevated levels of TN-C have been suggested to induce inflammatory mediators and promote ECM degradation in OA patients [39]. Although TN-C is highly expressed during embryogenesis, its presence is minimal in healthy adult tissues.…”

“…Its expression during OA is, however, highly upregulated [40, 41]. The elevated concentration of TN-C causes a significant effect in the catabolism of the cartilage, resulting in degradation of ECM [39, 40]. Additionally, biglycan fragments in articular cartilage and meniscus and fibronectin fragments in hip and knee synovia have also been found in elevated levels as OA progresses [42–44].…”

Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

“…Tenascin C is an extracellular glycoprotein involved in tissue injury/repair and is upregulated in osteoarthritic cartilage, where tenascin C protein fragments are believed to induce inflammatory mediators and ECM degradation (Patel et al, 2011; Sofat et al, 2012). We found no evidence of tenascin C fragmentation in Matn 3 V194D and Comp DelD469 samples since the examination of matched peptides did not reveal any genotype specific differences in sequence coverage (data not shown).…”

Dextran sulfate sodium-induced colitis mice up-regulated extracellular matrix tenascin-C

“…But, these molecules are reappeared in a diverse condition such as tissue injury, wound healing, vascular disease, tumorigenesis and metastasis. Tenascin-C is a modular, multifunctional extracellular matrix (ECM) glycoprotein that is associated with tissue injury and repair (Patel et al, 2011). 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 (Chiquet-Ehrismann et al, 2003;Patel et al, 2011).…”

“…Tenascin-C is a modular, multifunctional extracellular matrix (ECM) glycoprotein that is associated with tissue injury and repair (Patel et al, 2011). 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 (Chiquet-Ehrismann et al, 2003;Patel et al, 2011). Recent scientific evidences suggested that mucosal TnC is increased in ulcerative colitis and Crohn's disease, especially in areas of ulceration (Geboes et al, 2001), and sera of patients with active ulcerative colitis and Crohn's disease (Riedl et al, 2001).…”