SIRT1 antisense long noncoding RNA attenuates interleukin-1β-induced osteoarthritic gene expression in human...

Recent studies demonstrated the role of antisense long noncoding RNAs (AS lncRNAs) in regulating gene expression at the transcriptional or translational level. In this study, we assessed the effects of sirtuin 1 (SIRT1) AS lncRNA overexpression and inhibition, along with overexpression of miR-34a, on interleukin (IL)-1β-induced gene expression alterations in human chondrocytes, aiming to understand its role in human chondrocytes. We analyzed gene expression alterations using real-time PCR and assessed SIRT1 protein level alterations through western blotting. IL-1β stimulation significantly upregulated A disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS-5) and matrix metalloproteinase 13 (MMP-13). SIRT1 AS lncRNA overexpression significantly inhibited IL-1β-induced upregulation of these genes, whereas SIRT1 AS lncRNA inhibition further increased their expression. Moreover, overexpression of miR-34a significantly increased IL-1β-induced upregulation of ADAMTS-5 and MMP-13 which were rescued by over expression of SIRT1 AS lncRNA. SIRT1 protein levels were significantly increased by SIRT1 AS lncRNA overexpression and significantly reduced by its inhibition. Ribonuclease protection assay indicated the complete binding of SIRT1 AS lncRNA to SIRT1 mRNA. In the osteoarthritis (OA) cartilage, SIRT1 AS lncRNA expression was significantly reduced compared with that in normal cartilage. Our observations indicate that the binding of SIRT1 AS lncRNA to SIRT1 mRNA may suppress IL-1β-induced expression of cartilage-degrading enzymes. Therefore, SIRT1 AS lncRNA may be a novel therapeutic target for OA treatment.