PMID: 32141427Mar 7, 2020Paper

AGT, targeted by miR-149-5p, promotes IL-6-induced inflammatory responses of chondrocytes in osteoarthritis via activating JAK2/STAT3 pathway

Clinical and Experimental Rheumatology
Wenji WangHui Zhao

Abstract

Angiotensinogen (AGT) and miR-149-5p were differentially expressed genes in the osteoarthritis (OA), but their functional contribution to this disease is unclear. Our study aimed to illustrate their relevance to OA pathology and chondrocytic inflammation responses. In this study, a total of 32 healthy donors and 56 OA patients were recruited for cartilage tissues, and interleukin (IL)-6-stimulated human chondrocyte-articular (HC-a) cells were used as an in vitro OA model. RT-qPCR and western blot assays demonstrated that AGT was upregulated in OA cartilage tissues while miR-149-5p was downregulated. Using a loss-of-function assay and inhibitor treatment, we found that AGT knockdown inhibited the increase of IL-1β, matrix metalloproteinase (MMP)-13 and nitrite in IL-6-induced chondrocytes through blocking the renin-angiotensin system (RAS). The prediction (TargetScan) and validation (mutant and luciferase reporter assays) of the interaction between AGT and miR-149-5p indicated that miR-149-5p directly regulated inflammatory responses in OA chondrocytes by binding to AGT. Furthermore, using overexpression and inhibitor treatment experiments, our study proved that JAK2/STAT3 was activated in OA tissues, and AGT regulated OA inflam...Continue Reading

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