GW842166X Alleviates Osteoarthritis by Repressing LPS-mediated Chondrocyte Catabolism in Mice

作     者：Wan-ran HUANG Jun-xue TU Ai-qing QIAO Li-jia CHEN Wan-ran HUANG;Jun-xue TU;Ai-qing QIAO;Li-jia CHEN

作者机构：Department of PharmacyThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou325000China 

出 版 物：《Current Medical Science》 (当代医学科学（英文）)

年 卷 期：2022年第42卷第5期

页      面：1046-1054页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：GW842166X lipopolysaccharide osteoarthritis chondrocyte catabolism cartilage extracellular matrix 

摘      要：Objective To explore the role and underlying mechanism of GW842166X on osteoarthritis and osteoarthritis-associated abnormal *** 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 *** cytotoxicity of GW842166X was tested using the CCK-8 *** blot,RT-qPCR,and ELISA were applied to evaluate the expression of the inflammatory biomarkers in mouse *** expression of extracellular matrix molecules was detected by the Western blot,RT-qPCR,and ***,the activity of NF-κB was checked by the Western blot and *** mouse Hulth models were generated to examine the in vivo effects of GW842166X on *** and eosin staining,safranin O/fast green staining,and immunohistochemistry were applied to detect the histological *** GW842166X below 200µmol/L had no cytotoxicity on the mouse ***-induced high expression of TGF-β1,IL-10,TNF-α,and IL-6 was significantly reduced by *** addition,GW842166X upregulated the expression of aggrecan and collagen type III,which was downregulated after the LPS *** upregulated expression of ADAMTS-5 and MMP-13 by LPS stimulation was dropped in response to the GW842166X ***,LPS decreased the IκBαexpression in the cytoplasm and increased the nuclear p65 ***,these changes were reversed by the GW842166X ***,the damages in the knees caused by the Hulth surgery in mice were restored by *** GW842166X impeded the LPS-mediated catabolism in mouse chondrocytes,thereby inhibiting the progression of osteoarthritis.