期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 159, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2021.112772
关键词
BPA; Osteocytes; Pyroptosis; NLRP3; ROS
资金
- Natural Science Foundation of Zhejiang Province [LY21H060001]
- National Natural Science Foundation of China [81700936]
- Zhejiang Public Welfare Technology Application Research Project [LGF18H060006]
BPA induces pyroptotic death of osteocytes via the ROS/NLRP3/Caspase-1 pathway, increasing apoptosis and up-regulating protein expressions related to inflammation and cell damage. The oxidative stress and mitochondrial dysfunction caused by BPA are reversed by ROS scavengers and mitochondrial antioxidants, highlighting potential therapeutic targets for BPA-induced bone cell damage.
Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is commonly used as a plasticizer to manufacture various food packaging materials. Evidence has demonstrated that BPA disturbed bone health. However, few studies focused on the effect of BPA on osteocytes, making up over 95% of all the bone cells. Here, we reported that BPA inhibited the cell viability of MLO-Y4 cells, and increased apoptosis in a dose-dependent manner. Furthermore, BPA up-regulated protein expressions of speck-like protein containing CARD (ASC), NLRP3, cleaved caspase-1 (Casp-1 p20) and cleaved gasdermin D (GSDMD-N), and increased the ratios of interleukin (IL)-113/pro-IL-113 and IL-18/pro-IL-18 in MLO-Y4 cells. BPA enhanced levels of lactate dehydrogenase (LDH), IL113 and IL-18 in culture supernatants. This pyroptotic death and the NLPR3 inflammasome activation were reversed by the caspase-1 inhibitor VX765 or the NLRP3 inflammasome inhibitor MCC950. Furthermore, BPA stimulated the production of intracellular reactive oxygen species (ROS), mitochondrial ROS (mtROS), elevated malondialdehyde (MDA) level and decreased superoxide dismutase (SOD) activity, which led to oxidative damage in MLO-Y4 cells. The ROS scavenger N-acetylcysteine (NAC) or the mitochondrial antioxidant MitoTEMPO inhibited the NLPR3 inflammasome activation and pyroptotic death induced by BPA. Collectively, our data suggest that BPA causes pyroptotic death of osteocytes via ROS/NLRP3/Caspase-1 pathway.
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