文献类型：期刊文献

英文题名：ROS-mediated mitophagy and necroptosis regulate osteocytes death caused by TCP particles in MLO-Y4 cells

作者：Yang, Pei[1];Xu, Bingbing[1];Zhu, Ruirong[1];Zhang, Tao[1];Wang, Zihan[1];Lin, Qiao[1];Yan, Ming[2];Yu, Zhangsen[1];Mao, Hongjiao[1];Zhang, Yun[1]

机构：[1]Shaoxing Univ, Coll Med, Huancheng West Rd 508, Shaoxing 312000, Peoples R China;[2]Hangzhou Dianzi Univ, Sch Automat, 1158 2nd Ave, Hangzhou 310018, Peoples R China

年份：2023

卷号：496

外文期刊名：TOXICOLOGY

收录：SCI-EXPANDED(收录号：WOS:001104852800001)、、Scopus(收录号：2-s2.0-85170223243)、WOS

基金：This work was supported by Natural Science Foundation of Zhejiang Province (LY21H060001, LTGY23H180009), National Natural Science Foundation of China (30900301, 81700936), National College Students Innovation and Entrepreneurship Training Program (202210349028) and Undergraduate Scientific and Technological Innovation Project in Zhejiang Province (2023R465021).

语种：英文

外文关键词：TCP particles; Osteocytes; Mitophagy; Necroptosis; Reactive oxygen species

外文摘要：Our previous data have revealed TCP particles caused cell death of osteocytes, comprising over 95 % of all bone cells, which contribute to periprosthetic osteolysis, joint loosening and implant failure, but its mechanisms are not fully understood. Here, we reported that TCP particles inhibited cell viability of osteocytes MLO-Y4, and caused cell death. TCP particles caused mitochondrial impairment and increased expressions of LC-3 II, Parkin and PINK 1, accompanied by the elevation of autophagy flux and intracellular acidic components, the accumulation of LC-3II, PINK1 and Parkin in damaged mitochondria, and p62 reduction. The increased LC-3II expression and cell death extent were significantly enhanced by the autophagy inhibitor Baf A1, compared with Baf A1 (or TCP particles) alone, indicating that TCP particles increase autophagic flux and lead to cell even death of MLO-Y4 cells, closely associated with mitophagy. Furthermore, TCP particles induced propidium iodide (PI) uptake and the phosphorylation of RIP1, RIP3 and MLKL, thereby increasing necroptosis in MLO-Y4 cells. The pro-necroptotic effect was alleviated by the RIP1 inhibitor Nec-1 or the MLKL inhibitor NSA. Additionally, TCP particles promoted the production of intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS), and increased TXNIP expression, but decreased protein levels of TRX1, Nrf2, HO-1 and NQO1, leading to oxidative stress. The ROS scavenger NAC remarkably reversed mitophagy and necroptosis caused by TCP particles, suggesting that ROS is responsible for mitophagy and necroptosis. Collectively, ROS-mediated mitophagy and necroptosis regulate osteocytes death caused by TCP particles in MLO-Y4 cells, which enhances osteoclastogenesis and periprosthetic osteolysis.