Deficiency of tenascin-C delays articular cartilage repair in mice.

OBJECTIVE: In human articular cartilage, tenascin-C (TN-C) expression decreases during maturation of chondrocytes, and almost disappears in adults; however, it reappears in damaged cartilage. To examine the effects of TN-C on cartilage degeneration and repair, we compared articular cartilage degeneration between wild-type (WT) and tenascin-C knockout mouse (TNKO) mice using a spontaneous osteoarthritis (OA) in aged joints and surgical OA model. In addition, we made full-thickness cartilage defects and compared the cartilage repair process between the two groups. METHODS: The surgical procedure to create degenerative OA model was performed by transecting the anterior cruciate ligament and medial collateral ligament. Full-thickness defects were created in the center of the femoral trochlea to evaluate cartilage repair. Sections of cartilage were stained with hematoxylin and eosin or safranin-O, and immunostaining for TN-C. The degrees of degeneration and repair were graded. RESULTS: In the WT surgical OA model, the articular cartilage was almost normal at 2 weeks, but safranin-O decreased staining at 4 weeks. In TNKO mice, safranin-O decreased staining at 2 weeks, and cartilage was injured intensely at 4 weeks. In the cartilage repair model, TN-C was expressed after 1 week, was strongly expressed in the upper layer of regenerated tissue after 3 weeks, and disappeared after 6 weeks. The defects were restored until 6 weeks in WT mice; however, defects in TNKO mice were filled with fibrous tissue with no cartilage-like tissue. CONCLUSIONS: 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.

Changes in biochemical markers and prediction of effectiveness of intra-articular hyaluronan in patients with knee osteoarthritis.

OBJECTIVE: Intra-articular injection of hyaluronan (HA) is frequently used to treat knee osteoarthritis (OA). We studied whether HA injections induced significant changes in levels of biochemical markers in synovial fluid (SF). In addition, we investigated the possibility of predicting the effectiveness of HA based on these biochemical markers. METHODS: Twenty-eight patients with knee OA underwent five weekly intra-articular injections of HA. Knee pain was measured on visual analog scale (VAS) before and after the five injections. Levels of biochemical markers, including chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), keratan sulfate (KS), and tenascin-C (TN-C), were determined before and after the five injections. Correlations between the biochemical markers before HA injection and the improvement of VAS after the five injections were evaluated. RESULTS: After HA injections, levels of C6S, C4S, and KS decreased significantly. Inverse correlations were observed between the levels of TN-C and C4S before HA injection and improvement of VAS after the five injections. In contrast, no significant correlation was seen between levels of C6S and KS before injections and improvement of VAS after the five injections. CONCLUSION: 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.