文献类型：期刊文献

英文题名：Theaflavin-3,3′-Digallate Inhibits Erastin-Induced Chondrocytes Ferroptosis via the Nrf2/GPX4 Signaling Pathway in Osteoarthritis

作者：Xu, Chao[1];Ni, Su[2];Xu, Nanwei[3];Yin, Guangrong[4];Yu, Yunyuan[5];Zhou, Baojun[6];Zhao, Gongyin[3];Wang, Liangliang[3];Zhu, Ruixia[3];Jiang, Shijie[3];Wang, Yuji[3,6,7]

第一作者：Xu, Chao

通信作者：Wang, YJ[1];Wang, YJ[2];Wang, YJ[3]

机构：[1]Nanjing Med Univ, Affiliated Changzhou 2 Peoples Hosp, Truma Cent, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[2]Nanjing Med Univ, Affiliated Changzhou 2 Peoples Hosp, Med Res Ctr, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[3]Nanjing Med Univ, Affiliated Changzhou 2 Peoples Hosp, Changzhou Peoples Hosp 2, Changzhou Med Ctr,Dept Orthoped, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[4]Dalian Med Univ, Grad Sch, 9 West Sect,Shunnan Rd, Dalian 116044, Peoples R China;[5]Nanjing Med Univ, Affiliated Changzhou 2 Peoples Hosp, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[6]Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China;[7]Mayo Clin, Dept Orthoped Surg & Biochem & Mol Biol, Rochester, MN 55902 USA

第一机构：Nanjing Med Univ, Affiliated Changzhou 2 Peoples Hosp, Truma Cent, 29 Xinglong Alley, Changzhou 213003, Peoples R China

通信机构：[1]corresponding author), Nanjing Med Univ, Affiliated Changzhou 2 Peoples Hosp, Changzhou Peoples Hosp 2, Changzhou Med Ctr,Dept Orthoped, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China;[3]corresponding author), Mayo Clin, Dept Orthoped Surg & Biochem & Mol Biol, Rochester, MN 55902 USA.|[10735]甘肃中医药大学;

年份：2022

卷号：2022

外文期刊名：OXIDATIVE MEDICINE AND CELLULAR LONGEVITY

收录：;EI(收录号：20224913210406);Scopus(收录号：2-s2.0-85142788267);WOS:【SCI-EXPANDED(收录号:WOS:000891181700001)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (81171680 to Y.W.), the Science and Technology Support Program of Jiangsu Province (BE2015632to Y.W.), the Changzhou Science and Technology Bureau (ZD202217 to Y.W., CJ20180057 to S.N., and WZ202204 to C.X), the Natural Science Foundation of the Jiangsu for Youth (BK20180182 to S.N.), China Postdoctoral Science Foundation (2019M651898 to S.N.), Changzhou No. 2. People's Hospital Foundation (2022K004 to C.X.). We want to thank all the patients who participated in our study and Professors Xianju Zhou, Dawei Li, and Stephen Rudnik for giving suggestions.

语种：英文

外文关键词：Cartilage - Cell death - Lipids - Magnetic resonance imaging - Oxidation - Signaling

摘要：There is evidence that osteoarthritis (OA) is associated with ferroptosis which is a kind of lipid peroxidation-related cell death. Theaflavin-3,3 & PRIME;-digallate(TF3), a polyphenol compound extracted from black tea, possesses antioxidative and anti-inflammatory properties, but its effects on chondrocyte ferroptosis in osteoarthritis (OA) remain unclear. Our present study aims at exploring the protective role and underlying mechanisms of TF3 against erastin-induced chondrocyte ferroptosis in OA. In human primary chondrocytes treated with erastin alone or combined with different doses of TF3, cell viability was assessed by MTS. Ferroptosis-related proteins, including Gpx4, HO-1, and FTH1, were detected by western blot. The levels of lipid peroxidation and Fe2(+) were determined by fluorescence staining. Meanwhile, the change of related proteins in the Nrf2/Gpx4 signaling pathway was determined by western blot. siRNA-mediated Nrf2 knockdown and the Gpx4 inhibitor RSL3 were used to explore molecular mechanisms for TF3-induced ferroptosis in OA chondrocyte. The magnetic resonance imaging (MRI), HE staining, Masson's staining, and immunohistochemistry were used to evaluate articular cartilage damages in the rat OA model. The results showed that Gpx4 expression was markedly downregulated in the chondrocytes of OA patients. TF3 reversed erastin-induced ferroptosis of human cultured chondrocytes, lipid ROS, and Fe2(+) production in mitochondria. Moreover, the expression of Gpx4, HO-1, FTH1, and Nrf2 was markedly induced by TF3 in the erastin-treated chondrocytes. The antiferroptotic effect of TF3 was related to enhance Nrf2/Gpx4 signaling pathway. Finally, TF3 inhibited OA progression by alleviating in vivo cartilage damage related to chondrocyte ferroptosis. Thus, TF3 significantly inhibits chondrocyte ferroptosis by activating the Nrf2/Gpx4 signaling pathway, suggesting that TF3 serves as a potential therapeutic supplement for OA treatment.