Background The antisense cerebellar degenerative-related protein-1 (CDR1as) has been identified as a sponge for several microRNAs. MiR-641 has been shown to be downregulated in osteoarthritic human chondrocytes, but its regulation and function in osteoarthritis (OA) has not been reported. Methods OA cartilage samples were obtained from the knee joints of 12 patients (8 males and 4 females at age of 57-73 years old) who underwent total knee arthroplasty. Normal articular cartilage samples were obtained from the knee joints of 10 trauma patients at age of 29-65 years old (6 males and 4 females). The levels of circRNA-CDR1as mRNA and miR-641 were examined by qRT-PCR and the contents of type II collagen (Col II), IL-6, MMP13 and GAPDH in chondrocytes were examined by Western blot. Results In this study, we found that circRNA-CDR1as level was significantly upregulated in OA chondrocytes, and negatively related with that of miR-641. RNA pull down assay confirmed that circRNA-CDR1as directly targets to miR-641. Furthermore, downregulation of circRNA-CDR1as increased type II collagen level but reduced MMP13 and IL-6 contents, while these effects were partly reversed by down-regulation of miR-641. Conclusion Overall, our results indicate that circRNA-CDR1as plays a crucial role in regulating OA progression via modulating extracellular matrix metabolism and inflammation via sponging miR-641 and provide a novel regulatory role of circRNA-CDR1as in OA.

中文翻译：

---

环状 RNA-CDR1as 充当 microRNA-641 的海绵，促进骨关节炎进展。

背景 反义小脑退行性相关蛋白 1 (CDR1as) 已被确定为几种 microRNA 的海绵。已显示 MiR-641 在骨关节炎人类软骨细胞中下调，但尚未报道其在骨关节炎 (OA) 中的调节和功能。方法 取12例（男8例，女4例，年龄57～73岁）全膝关节置换术患者的膝关节OA软骨标本。正常关节软骨样本取自 10 名年龄在 29-65 岁的外伤患者（6 名男性和 4 名女性）的膝关节。qRT-PCR检测circRNA-CDR1as mRNA和miR-641的水平，Western blot检测软骨细胞中II型胶原（Col II）、IL-6、MMP13和GAPDH的含量。结果 在这项研究中，我们发现 circRNA-CDR1as 水平在 OA 软骨细胞中显着上调，与 miR-641 呈负相关。RNA pull down 试验证实 circRNA-CDR1as 直接靶向 miR-641。此外，circRNA-CDR1as 的下调增加了 II 型胶原蛋白的水平，但降低了 MMP13 和 IL-6 的含量，而这些影响被 miR-641 的下调部分逆转。结论 总体而言，我们的研究结果表明，circRNA-CDR1as 通过调节细胞外基质代谢和炎症，通过海绵化 miR-641 在调节 OA 进展中起关键作用，并提供了 circRNA-CDR1as 在 OA 中的新调节作用。circRNA-CDR1 的下调增加了 II 型胶原蛋白的水平，但降低了 MMP13 和 IL-6 的含量，而这些影响被 miR-641 的下调部分逆转。结论 总体而言，我们的研究结果表明，circRNA-CDR1as 通过调节细胞外基质代谢和炎症，通过海绵化 miR-641 在调节 OA 进展中起关键作用，并提供了 circRNA-CDR1as 在 OA 中的新调节作用。circRNA-CDR1 的下调增加了 II 型胶原蛋白的水平，但降低了 MMP13 和 IL-6 的含量，而这些影响被 miR-641 的下调部分逆转。结论 总体而言，我们的研究结果表明，circRNA-CDR1as 通过调节细胞外基质代谢和炎症，通过海绵化 miR-641 在调节 OA 进展中起关键作用，并提供了 circRNA-CDR1as 在 OA 中的新调节作用。