Research Paper Volume 11, Issue 10 pp 3348—3361
circFADS2 protects LPS-treated chondrocytes from apoptosis acting as an interceptor of miR-498/mTOR cross-talking
- 1 , Department of Rheumatology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu 225000, China
- 2 , Clinical Medical College, Dalian Medical University, Jiangsu 225000, China
- 3 , Medical College of Yangzhou University, Jiangsu 225000, China
- 4 , Department of Physiology, School of Medicine, Showa University, Jiangsu 225000, China
- 5 , Department of Pathology, Clinical Medical College, Yangzhou University, Jiangsu 225000, China
Received: December 20, 2018 Accepted: May 17, 2019 Published: May 29, 2019https://doi.org/10.18632/aging.101986
How to Cite
Copyright: Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
We aimed to investigate the regulation of circular RNAs in lipopolysaccharide (LPS)-treated chondrocytes isolated from SD rat. In this study, we analyzed how circFADS2 was regulated in LPS-treated chondrocytes and isolates from Rheumatoid arthritis (RA) patients and found that circFADS2 and mTOR were highly expressed whereas miR-498 expression was significantly reduced. We then silenced circFADS2 in LPS-treated chondrocytes; this resulted in a declined expression of type II collagen, but an increase in the expression of MMP-13, COX-2, and IL-6. Overall, silencing circFADS2 caused a significant reduction in the proliferative rate of LPS-treated chondrocytes, increased apoptotic levels, miR-498 upregulation, and mTOR downregulation. Dual-luciferase reporter assay indicated that circFADS2 directly targeted miR-498. In contrast, miR-498 down-regulation affected circFADS2 silencing, promoting extracellular matrix (ECM) degradation and apoptosis. The 3’ UTR of the mTOR gene is targeted by miR-498, and consequently, in cells transfected with miR-498, there was a significant reduction of mTOR expression at the protein and mRNA levels. Silencing mTOR had a similar effect to circFADS2 silencing on type II collagen, MMP-13, COX-2, and IL-6 expression, as well as cell proliferation and apoptosis. In conclusion, circFADS2 may affect LPS-induced chondrocytes properties by regulating the ECM catabolism, inflammation, and apoptosis in chondrocytes.