This study revealed that cartilage repair in TNKO mice was significantly slower than that in WT mice and that the deficiency of TN-C progressed during cartilage degeneration.

Local generation of thrombin-cleaved OPN was increased in RA joints. Thrombin-cleaved OPN may be a useful biochemical marker of RA.

Tenascin-C (TN-C) is a hexameric glycoprotein component of extracellular matrix, and alternative RNA splicing creates two major TN-C size variants (the small and large variants). The large TN-C variants play key roles in many pathologic conditions in adults, including tumorigenesis, regeneration, and inflammation. This cross-sectional study compared levels of large TN-C variants in synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Synovial fluid samples were obtained from knees of 26 patients with advanced RA and 79 with advanced OA. Expression of TN-C splice variants was examined using Western blotting. The levels of large TN-C variants in synovial fluid were determined by an enzyme-linked immunosorbent assay. Synovium were analyzed for TN-C by immunohistochemistry. Immunoblotting showed the presence of large TN-C variants in synovial fluid from patients with RA and OA. However, levels of large TN-C variants were fourfold higher in RA samples compared with OA samples (p < 0.01). Synovial fluid levels of TN-C in RA did not correlate with C-reactive protein levels. Immunohistochemistry of the synovium showed stronger reactivity in RA samples than in OA samples. These results indicate that local synthesis of TN-C is increased during rheumatic disease. ß

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The reduction in C6S, C4S, and KS levels after HA injections reflects that HA could help maintain normal cartilage metabolism. Our findings suggest that HA injections are effective in patients whose knees contain low levels of TN-C and C4S, reflecting an early stage of OA and limited synovitis.