Circular RNA-CDR1as acts as the sponge of microRNA-641 to promote osteoarthritis progression

J Inflamm (Lond). 2020 Feb 18:17:8. doi: 10.1186/s12950-020-0234-y. eCollection 2020.

Abstract

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.

Keywords: Extracellular matrix; Osteoarthritis; circRNA-CDR1as; miR-641.