Osteopontin(OPN)alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes

查看全文 作　　者：Wei [1,2]Luo;Zili [1,2]Lin;Yuhao [1]Yuan;Ziyi [1]Wu;Wei [1]Zhong;Qing [1,2]Liu

机构地区：[1]Department of Orthopaedics,Xiangya Hospital,Central South University,Changsha,Hunan 410008,China;[2]National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Changsha,Hunan 410008,China

出　　处：《Genes & Diseases》索引2023年第10卷第4期,共12页

基　　金：supported by the Special funds for the con-struction of innovative provinces in Hunan Province(No.2020RC3058);the Natural Science Foundation of Hunan(No.2022JJ40802,2022JJ30075);the China Post-doctoral Science Foundation(No.2022M713525). 摘　　要：Osteoarthritis(OA)is a chronic debilitating joint disease,characterized by degen-eration of the cartilage and loss of the cartilage matrix,and it is clinically manifested as joint pain.Osteopontin(OPN)is a glycoprotein that is abnormally expressed in the bone and carti-lage tissues and plays a vital role in various pathological processes such as the osteoarthritic inflammatory response and endochondral ossification.The focus of our study is to investigate the therapeutic potential and specific role of OPN in OA.Using morphological comparisons,we found that the cartilage was severely worn-out and there was a significant loss of the cartilage matrix in OA.OPN,CD44,and hyaluronic acid(HA)synthase 1(HAS1)were highly expressed,and the anabolism of HA was significantly higher in the OA chondrocytes than in the control chondrocytes.Additionally,we treated the OA chondrocytes with small interfering RNA(siRNA)targeting OPN,recombinant human OPN(rhOPN),and a combination of rhOPN and anti-CD44 antibodies.Furthermore,in vivo experiments were performed in mice.We found that OPN up-regulated the expression of downstream HAS1 and increased the anabolism of HA through CD44 protein expression in OA mice compared with those in control mice.Moreover,intra-articular injection of OPN in mice with OA significantly inhibited OA progression.In summary,OPN ini-tiates an intracellular cascade via CD44 which results in an anabolic increase in HA levels,thereby inhibiting OA progression.Therefore,OPN is a promising therapeutic agent in precision treatment of OA. 关键词：Cartilage degeneration CD44 Hyaluronic acid OSTEOARTHRITIS OSTEOPONTIN

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Osteopontin(OPN)alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes

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