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  • Title: DUSP19 regulates IL-1β-induced apoptosis and MMPs expression in rat chondrocytes through JAK2/STAT3 signaling pathway.
    Author: Yao ZZ, Hu AX, Liu XS.
    Journal: Biomed Pharmacother; 2017 Dec; 96():1209-1215. PubMed ID: 29174854.
    Abstract:
    Osteoarthritis (OA) is a disease with degeneration of articular cartilage and its development and progression is characterized by chondrocyte apoptosis. To examine whether DUSP19 and inhibitor of the JAK2/STAT3 will influence the response of rat chondrocytes cultured with IL-1β. Dose-response studies were conducted under IL-1β conditions. In separate experiments, chondrocytes were treated with an appropriate concentration of IL-1β with either DUSP19-expressing constructs or AG490, whereas chondrocytes were also treated with DUSP19-RNA interference constructs with or without AG490. The expression of DUSP19, apoptosis markers, JAK2/STAT3 and phosphorylation of JAK2/STAT3 was measured by Real-time PCR and/or western blot assay. CCK-8 assay and Annexin V/propidium iodide staining was used to detect chondrocyte viability and apoptosis, respectively. IL-1β dose-dependently decreased the expression of DUSP19 and the viability of chondrocytes. Chondrocytes with DUSP19 up-regulation inhibited IL-1β-induced increases in the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 expression as well as cell apoptosis. However, DUSP19 down-regulation mimicked the effect of IL-1β on JAK2/STAT3 activity and chondrocyte apoptosis. AG490 inhibited JAK2/STAT3 activation as well as apoptosis in chondrocytes induced by IL-1β or DUSP19 down-regulation, evidenced by decreased expression of Bax, Caspase-3 and increased Bcl-2 expression as well as MMP-3, -9 and -13 expressions. Taken together, our results demonstrate that DUSP19 up-regulation inhibited IL-1β-induced chondrocytes apoptosis and MMPs expression through inactivating JAK2/STAT3 pathway.
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