Foxo3a aggravates inflammation and induces apoptosis in IL-1-treated rabbit chondrocytes via positively regulating tenascin-c

Abstract

Introduction. Osteoarthritis (OA) is the most common degenerative disease in middle-aged and elderly individuals that causes joint deformity and limb disability. Accumulating evidence has suggested that the pathogenesis of OA has been related to various mechanisms such as apoptosis, inflammation, oxidative stress and metabolic disorders. The aim of this study is to clarify the role of Foxo3a in the progress of OA in an in vitro model. Materials and methods. The chondrocytes were derived from rabbit, and treated with IL-1b, which was used as an in vitro OA model. The over-expression and down-regulation of Foxo3a were achieved by transfection with overexpression vector or shRNA, respectively. The mRNA level of iNOS in chondrocytes was quantified by qPCR. Tenascin-c (Tnc) production was measured by ELISA and apoptosis-associated proteins were analyzed by Western blotting. The MTT assay was used to assess the viability of chondrocytes. Results. Foxo3a and iNOS expression were upregulated in IL-1b-treated chondrocytes. Foxo3a silencing decreased iNOS expression, and inhibited apoptosis of IL-1b-treated chondrocytes. The production of Tnc was significantly increased in IL-1b-treated chondrocytes and was positively regulated by Foxo3. Importantly, extracellular addition of Tnc abrogated the protective effects of Foxo3a knockdown on IL-1b -treated chondrocytes. Conclusion. The present study indicated that down-regulation of Foxo3a protected IL-1b-treated chondrocytes by decreasing iNOS expression and suppressing chondrocytes' apoptosis via modulating tenascin-c, which could be regarded as a potent therapeutic target for the treatment of OA.

Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis

“…Furthermore, IL-1β causes synoviocytes and chondrocytes to secrete degenerative enzymes such as MMPs. The cytokine receptors on articular chondrocyte surfaces are activated by IL-1β, which leads to the activation of the NF-κB signaling pathway [ 31 , 32 ]. This signaling pathway inhibits chondrocyte anabolic activity, either alone or in conjunction with other signaling pathways [ 33 ].…”

“…In OA joints, IL-1β can trigger apoptosis of chondrocytes [ 34 ]. Furthermore, when human chondrocytes from normal and OA cartilage were treated with human IL-1β, apoptosis increased [ 31 ]. Similarly, through DCF fluorescence, we showed that IL-1β incubation increased ROS production.…”