Progranulin regulation of autophagy contributes to its chondroprotective effect in osteoarthritis

作     者：Yiming Pan Yuyou Yang Mengtian Fan Cheng Chen Rong Jiang Li Liang Menglin Xian Biao Kuang Nana Geng Naibo Feng Lin Deng Wei Zheng Fengmei Zhang Xiaoli Li Fengjin Guo Yiming Pan;Yuyou Yang;Mengtian Fan;Cheng Chen;Rong Jiang;Li Liang;Menglin Xian;Biao Kuang;Nana Geng;Naibo Feng;Lin Deng;Wei Zheng;Fengmei Zhang;Xiaoli Li;Fengjin Guo

作者机构：Department of Cell Biology and GeneticsCore Facility of Development BiologyChongqing Medical UniversityChongqing 400016China Department of OrthopaedicsThe 1st Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Laboratory of Stem Cells and Tissue EngineeringChongqing Medical UniversityChongqing 400016China Department of OrthopaedicsThe 2nd Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Medical University Laboratory Animal CenterChongqing Medical UniversityChongqing 400016China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2023年第10卷第4期

页      面：1582-1595页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.81672209) Chongqing Science and Technology Bureau(No.cstc2020jcyj-msxmX0175),China Chongqing Human Resources and Social Security Bureau(No.2018-389),China. 

主　　题：Anabolism ATG12 ATG5 Autophagy Catabolism Osteoarthritis PGRN 

摘      要：Progranulin(PGRN)is a multifunctional growth factor involved in many physiolog-ical processes and disease states.The apparent protective role of PGRN and the importance of chondrocyte autophagic function in the progression of osteoarthritis(OA)led us to investi-gate the role of PGRN in the regulation of chondrocyte autophagy.PGRN knockout chondro-cytes exhibited a deficient autophagic response with limited induction following rapamycin,serum starvation,and IL-1b-induced autophagy.PGRN-mediated anabolism and suppression of IL-1b-induced catabolism were largely abrogated in the presence of the BafA1 autophagy inhibitor.Mechanistically,during the process of OA,PGRN and the ATG5eATG12 conjugate form a protein complex;PGRN regulates autophagy in chondrocytes and OA through,at least partially,the interactions between PGRN and the ATG5eATG12 conjugate.Furthermore,the ATG5eATG12 conjugate is critical for cell proliferation and apoptosis.Knockdown or knockout of ATG5 reduces the expression of ATG5eATG12 conjugate and inhibits the chondroprotective effect of PGRN on anabolism and catabolism.Overexpression of PGRN partially reversed this effect.In brief,the PGRN-mediated regulation of chondrocyte autophagy plays a key role in the chondroprotective role of PGRN in OA.Such studies provide new insights into the pathogen-esis of OA and PGRN-associated autophagy in chondrocyte homeostasis.