Prolonged Cadmium Exposure and Osteoclastogenesis: A Mechanistic Mouse and <i>in Vitro</i> Study
Zhiyuan Liu, Jinzhi Wu, Zhe Dong, Yanshuai Wang, Gang Wang, Chengjie Chen, Huihui Wang, Yang Yang, Yongxin Sun, Maowei Yang, Jingqi Fu, Jiliang Li, Qiang Zhang, Yuanyuan Xu, Jingbo Pi
Abstract
BACKGROUND: Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear. OBJECTIVES: We aimed to understand the molecular mechanisms underlying Cd-induced bone loss, focusing mainly on the roles of NRF2 and NRF1 in osteoclastogenesis provoked by Cd. METHODS: ) with a combination of genetic and chemical modulations targeting NRF2 and NRF1. RESULTS: -KD cells. CONCLUSIONS: expression, osteoclastogenesis and thus bone homeostasis. Our study suggests a novel strategy targeting NRF2 and L-NRF1 to prevent and treat the bone toxicity of Cd. https://doi.org/10.1289/EHP13849.