Down-regulated ciRS-7/up-regulated miR-7 axis aggravated cartilage degradation and autophagy defection by PI3K/AKT/mTOR activation mediated by IL-17A in osteoarthritis

Xindie Zhou(Changzhou No.2 People's Hospital), Li Jin(Jiaxing University), Yuanshuai Zhou(Suzhou Institute of Biomedical Engineering and Technology), Zhicheng Yang(Nanjing Medical University), Haoyu Yang(Changzhou No.2 People's Hospital), Dong Li(Nanjing Medical University), Junjie Zhang(Changzhou No.2 People's Hospital), Yi Zhang(Nanjing Medical University), Nanwei Xu(Nanjing Medical University), Yong Huang(Changzhou No.2 People's Hospital), Lifeng Jiang(Second Affiliated Hospital of Zhejiang University)
Aging
October 25, 2020
Cited by 92Open Access
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Abstract

. Gene sequencing and bioinformatics analysis performed on a control group, IL-1β group, and IL-1β+miR-7-mimics group demonstrated that seven of the most significant mRNA candidates were enriched in the interleukin-17 (IL-17) signaling pathway. Increased IL-17A levels were also observed by qRT-PCR and ELISA. In addition, it was revealed that the ciRS-7/miR-7 axis ameliorated cartilage degradation and defection of autophagy by PI3K/AKT/mTOR activation in IL-1β-induced chondrocytes. Furthermore, an OA model was established in rats with medial meniscus destabilization. miR-7-siRNA-expressing lentiviruses alleviated surgical resection-induced cartilage destruction of OA mice, whereas miR-7 mimics worsened the effects. Thus, these findings revealed that the mechanism of the ciRS-7/miR-7 axis involved regulating OA progression and provided valuable directions for OA treatment.


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