著者

海野 宏至 長谷川 正裕 鈴木 慶亮 松井 佑梨世 湏藤 啓広 今中(吉田) 恭子 吉田 利通

出版者

日本関節病学会

雑誌

日本関節病学会誌 (ISSN:18832873)

巻号頁・発行日

vol.35, no.2, pp.131-136, 2016 (Released:2017-07-31)

参考文献数

16

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Objective: Tenascin-C (TNC) is an extracellular matrix glycoprotein. In this study, we examined the effects of full-length TNC on joint cartilage protection in murine osteoarthritis (OA) models and on synovial inflammation in OA joints. In addition, we performed an in vitro study to reveal the mechanism of repairing cartilage using full-length TNC.Methods: In this in vivo study, fourteen male BALB/c strain mice (8-weeks-old) were used. Both knee joints were exposed and the anterior cruciate ligament and medial collateral ligament were transected. 10 μg/mL of TNC were injected into the knee joint (group Ⅰ). The control group had injection of phosphate buffered saline (PBS) (group Ⅱ). Mice were sacrificed at 4 days, 2 weeks, and 4 weeks postoperatively. Cartilage was evaluated using the Mankin score, and synovitis was evaluated using the Synovitis score. An in vitro study was also performed on human cartilage specimens, which were obtained from patients who underwent total knee arthroplasty for the treatment of OA. Chondrocytes were isolated and cultured, and they were treated with 0, 1, or 10 μg/mL of TNC. We also compared the expression of many kinds of messenger RNA after exposure at each dose by real-time polymerase chain reaction. We evaluated the expression of TNC, inflammatory cytokines [TNF-α, IL-1β, NFκB], anabolic factors [TGFβ, TIMP3, bFGF], and catabolic factors [ADAMTS-4, -5, and MMP-3, -13].Results: With the in vivo study, the average Mankin scores were significantly better in group Ⅰ than group Ⅱ at 4 weeks (group Ⅰ; 1.1, group Ⅱ; 3.2 (P<0.05)). At 4 days and 2 weeks, no development of OA was found in either of the two groups. Low-grade synovitis occurred in both groups at 4 days, 2 weeks, and 4 weeks. There were no significant differences in average synovitis scores between two groups at 4 days, 2 weeks, and 4 weeks. The in vitro study revealed that TNC upregulated the expression of endogenous TNC, TNFα, IL-1β, NFκB, TGFβ, TIMP3 and ADAMTS-4, MMP-3, and MMP-13. But 10 μg/mL of TNC downregulated the expression of ADAMTS-5.Conclusion: This study has demonstrated that 10 μg/mL of full-length TNC can prevent articular cartilage degeneration for 4 weeks without promoting synovitis. The in vitro study demonstrated that TNC upregulates itself and anabolic factors. However, TNC also downregulated the expression of ADAMTS-5 which contributed to cartilage degradation.