Objective

TNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model.

Design

Ten micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis. The control group received an injection of phosphate buffered saline (group I). Synovitis was evaluated using synovitis score 2 and 4 weeks after injection. The ligaments of knee joints of mice were transected to make the osteoarthritis model. After transection, 10 µg/mL of TNIIIA2 was injected into the knee joint (group IV). The control group received an injection of phosphate buffered saline after transection (group III). Histologic examinations were made using hematoxylin and eosin and safranin-O staining at 2, 4, 8, and 12 weeks postoperatively. An in vitro study was also performed to determine the mechanism by which TNIIIA2 prevents cartilage degeneration. Human chondrocytes were isolated, cultured, and treated with TNIIIA2. The expressions of various mRNAs, including inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared using real-time polymerase chain reaction.

Results

There were no differences between groups in the study of intra-articular injection of mice (group I vs. group II). In the osteoarthritis model, we found development of osteoarthritis was suppressed in group IV at 4 and 8 weeks. TNIIIA2 upregulated the expressions of tumor necrosis factor-α, matrix metalloproteinase 3, and basic fibroblast growth factor.

Conclusion

We demonstrated that TNIIIA2 could prevent cartilage degeneration without synovitis.

中文翻译：

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TNIIIA2，肌腱蛋白-C 的肽，作为预防关节软骨退化的候选者

客观的

TNIIIA2 是细胞外基质糖蛋白肌腱蛋白-C 的肽。我们评估了关节内注射 TNIIIA2 是否可以在骨关节炎小鼠模型中预防关节软骨退化而不诱发滑膜炎。

设计

将每毫升 10 微克的 TNIIIA2 注射到小鼠（第 II 组）的膝关节中，以评估滑膜炎的诱发情况。对照组接受磷酸盐缓冲盐水注射（第一组）。在注射后 2 周和 4 周使用滑膜炎评分评估滑膜炎。横断小鼠膝关节韧带，制作骨关节炎模型。横断后，将 10 µg/mL 的 TNIIIA2 注入膝关节（IV 组）。对照组在横断后注射磷酸盐缓冲盐水（III组）。在术后 2、4、8 和 12 周使用苏木精、伊红和番红-O 染色进行组织学检查。体外_还进行了研究以确定TNIIIA2预防软骨退化的机制。用TNIIIA2分离、培养和处理人软骨细胞。使用实时聚合酶链反应比较了各种 mRNA 的表达，包括炎症细胞因子、软骨的合成代谢和分解代谢因子。

结果

在小鼠关节内注射研究中各组之间没有差异（I组与II组）。在骨关节炎模型中，我们发现在第 4 周和第 8 周时，IV 组的骨关节炎发展受到抑制。TNIIIA2上调肿瘤坏死因子-α、基质金属蛋白酶3和碱性成纤维细胞生长因子的表达。

结论

我们证明了 TNIIIA2 可以在没有滑膜炎的情况下预防软骨退化。