The role of NLRP3/Caspase-1/IL-1 β axis on the anti-osteoarthritis effect of resveratrol
Objective:Resveratrol is considered a potential candidate for the treatment of osteoarthritis(OA),but the mechanism of protection remains to be elucidated.The aim of this study was to investigate the effect of resveratrol on the NLRP3/Caspase-1/IL-1 β axis in high-fat diet(HFD)induced obesity-related OA,and to explore whether the effect of resveratrol on this axis is related to the activation of PI3K/AKT signaling pathway.Methods:Male C57BU6 mice were fed with a HFD or HFD plus resveratrol for 22 weeks.The knee joint samples were collected for histological,immunohistochemical,and PCR analyses.For in vitro experiments,SW1353 chondrosarcoma cells were treated with IL-1 β to mimic OA state,and LY294002,an inhibitor of PI3K,was used to block the PI3K/AKT signaling pathway.Then western blot analysis was used to detect the levels of protein expression.Results:Mice fed with HFD presented OA-like lesions in cartilage tissues,while resveratrol treatment alleviated this lesion.HFD upregulated the mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β,while additional resveratrol treatment downregulated them.Besides,the protein expression of NLRP3 and Caspase-1 decreased in the presence of LY294002 in IL-1 β-stimulated SW1353 cells,and additional resveratrol further downregulated their expression.However,compared with IL-1 β+RES group,LY294002 treatment had no significant effect on the expression of NLRP3 and Caspase-1.Conclusion:NLRP3/Caspase-1/IL-1β axis was activated in articular cartilage of mice with obesity-associated OA,and resveratrol exerted protective effect by reversing its activation.The inhibitory mechanism is independent of the PI3K/AKT signaling pathway.
NETL
NSTL
万方数据
