文献类型：期刊文献

英文题名：Fluoride Exposure Provokes Mitochondria-Mediated Apoptosis and Increases Mitophagy in Osteocytes via Increasing ROS Production

作者：Zhang, Yun[1];Dong, Fanhe[1];Wang, Zihan[1];Xu, Bingbing[1];Zhang, Tao[1];Wang, Qiqi[1];Lin, Qiao[1]

机构：[1]Shaoxing Univ, Coll Med, Huancheng West Rd 508, Shaoxing 312000, Peoples R China

年份：0

外文期刊名：BIOLOGICAL TRACE ELEMENT RESEARCH

收录：SCI-EXPANDED(收录号：WOS:000869591000002)、、Scopus(收录号：2-s2.0-85140128518)、WOS

基金：This work was supported by the Natural Science Foundation of Zhejiang Province (LY21H060001), the National Natural Science Foundation of China (30900301), and the National Undergraduate Innovation and Entrepreneurship Training Program (202110349006).

语种：英文

外文关键词：Fluoride; Osteocytes; Mitochondria; Apoptosis; Mitophagy; ROS

外文摘要：Fluoride is a persistent environmental pollutant, and its excessive intake causes skeletal and dental fluorosis. However, few studies focused on the effects of fluoride on osteocytes, making up over 95% of all bone cells. This study aimed to investigate the effect of fluoride on osteocytes in vitro, as well as explore the underlying mechanisms. CCK-8, LDH assay, fluorescent probes, flow cytometry, and western blotting were performed to examine cell viability, apoptosis, mitochondria changes, reactive oxygen species (ROS) and mitochondrial ROS (mtROS), and protein expressions. Results showed that sodium fluoride (NaF) exposure (4, 8 mmol/L) for 24 h inhibited the cell viability of osteocytes MLO-Y4 and promoted G0/G1 phase arrest and increased cell apoptosis. NaF treatment remarkably caused mitochondria damage, loss of MMP, ATP decrease, Cyto c release, and Bax/Bcl-2 ratio increase and elevated the activity of caspase-9 and caspase-3. Furthermore, NaF significantly upregulated the expressions of LC-3II, PINK1, and Parkin and increased autophagy flux and the accumulation of acidic vacuoles, while the p62 level was downregulated. In addition, NaF exposure triggered the production of intracellular ROS and mtROS and increased malondialdehyde (MDA); but superoxide dismutase (SOD) activity and glutathione (GSH) content were decreased. The scavenger N-acetyl-L-cysteine (NAC) significantly reversed NaF-induced apoptosis and mitophagy, suggesting that ROS is responsible for the mitochondrial-mediated apoptosis and mitophagy induced by NaF exposure. These findings provide in vitro evidence that apoptosis and mitophagy are cellular mechanisms for the toxic effect of fluoride on osteocytes, thereby suggesting the potential role of osteocytes in skeletal and dental fluorosis.