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gw842166x Alleviates Osteoarthritis by Repressing LPS-mediated Chondrocyte Catabolism in Mice

Current Medical Science 2022年第5期42卷 1046-1054页

作者： Wan-ran HUANG Jun-xue TU Ai-qing QIAO Li-jia CHEN Department of Pharmacy The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou325000China

Objective To explore the role and underlying mechanism of gw842166x on osteoarthritis and osteoarthritis-associated abnormal catabolism.Methods The extracted mouse chondrocytes were treated with gw842166x followed by lipopolysaccharide(LPS).The chondrocytes were divided into the control group,LPS group,LPS+50 nmol/L gw842166x group,and LPS+100 nmol/L gw842166x group.The cytotoxicity of gw842166x was tested using the CCK-8 assay.Western blot,RT-qPCR,and ELISA were applied to evaluate the expression of the inflammatory biomarkers in mouse chondrocytes.The expression of extracellular matrix molecules was detected by the Western blot,RT-qPCR,and immunofluorescence.Additionally,the activity of NF-κB was checked by the Western blot and immunofluorescence.The mouse Hulth models were generated to examine the in vivo effects of gw842166x on osteoarthritis.Hematoxylin and eosin staining,safranin O/fast green staining,and immunohistochemistry were applied to detect the histological changes.Results gw842166x below 200µmol/L had no cytotoxicity on the mouse chondrocytes.LPS-induced high expression of TGF-β1,IL-10,TNF-α,and IL-6 was significantly reduced by gw842166x.In addition,gw842166x upregulated the expression of aggrecan and collagen type III,which was downregulated after the LPS stimulation.The upregulated expression of ADAMTS-5 and MMP-13 by LPS stimulation was dropped in response to the gw842166x treatment.Furthermore,LPS decreased the IκBαexpression in the cytoplasm and increased the nuclear p65 expression.However,these changes were reversed by the gw842166x pretreatment.Moreover,the damages in the knees caused by the Hulth surgery in mice were restored by gw842166x.Conclusion gw842166x impeded the LPS-mediated catabolism in mouse chondrocytes,thereby inhibiting the progression of osteoarthritis.

关键词： gw842166x lipopolysaccharide osteoarthritis chondrocyte catabolism cartilage extracellular matrix

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