Progranulin regulation of autophagy contributes to its chondroprotective effect in osteoarthritis

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

作者地址："[Pan, Yiming; Yang, Yuyou; Fan, Mengtian; Liang, Li; Xian, Menglin; Geng, Nana; Feng, Naibo; Deng, Lin; Zheng, Wei; Li, Xiaoli; Guo, Fengjin] Chongqing Med Univ, Dept Cell Biol & Genet, Core Facil Dev Biol, Chongqing 400016, Peoples R China; [Chen, Cheng] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthopaed, Chongqing 400016, Peoples R China; [Jiang, Rong] Chongqing Med Univ, Lab Stem Cells & Tissue Engn, Chongqing 400016, Peoples R China; [Kuang, Biao] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthopaed, Chongqing 400016, Peoples R China; [Zhang, Fengmei] Chongqing Med Univ, Lab Anim Ctr, Chongqing 400016, Peoples R China"

通信作者："Guo, FJ (通讯作者)，Chongqing Med Univ, Dept Cell Biol & Genet, Core Facil Dev Biol, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001017327300001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：10

期号：4

开始页：1582

结束页：1595

文献类型：Article

关键词：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-1D-induced autophagy. PGRN-mediated anabolism and suppression of IL-1D-induced catabolism were largely abrogated in the presence of the BafA1 autophagy inhibitor. Mechanistically, during the process of OA, PGRN and the ATG5-ATG12 conjugate form a protein complex; PGRN regulates autophagy in chondrocytes and OA through, at least partially, the interactions between PGRN and the ATG5-ATG12 conjugate. Furthermore, the ATG5-ATG12 conjugate is critical for cell proliferation and apoptosis. Knockdown or knockout"

基金机构："National Natural Science Foundation of China [81672209]; Chongqing Science and Technology Bureau, China [cstc2020jcyj-msxmX0175]; Chongqing Human Resources and Social Security Bureau, China [2018-389]"

基金资助正文："This work was 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."