Yimin Dong, Honglei Kang, Renpeng Peng, Zheming Liu, Fuben Liao, Shi-An Hu, Weizhong Ding, Pengju Wang, Pengchao Yang, Meipeng Zhu, Sibo Wang, Minglong Wu, Dawei Ye, Xin Gan, Feng Li, Kehan Song
Activating Nrf2 by small molecules is a promising strategy to treat postmenopausal osteoporosis. However, there is currently no Nrf2 activator approved for treating chronic diseases, and the downstream mechanism underlying the regulation of Nrf2 on osteoclast differentiation remains unclear. Here, we found that bitopertin, a clinical-stage glycine uptake inhibitor, suppresses osteoclast differentiation and ameliorates ovariectomy-induced bone loss by activating Nrf2. Mechanistically, bitopertin interacts with the Keap1 Kelch domain and decreases Keap1-Nrf2 binding, leading to reduced Nrf2 ubiquitination and degradation...
March 28, 2024: Cell Metabolism