ABSTRACT
This study evaluated the effects of antimycin A (AMA), an inhibitor of electron transport in mitochondria, on the release of intracellular calcium ion ([Ca^2+^]~i~), ROS and bone resorbing factors in osteoblastic MC3T3‐E1 cells. Pretreatment of osteoblasts with trolox, a ROS scavenger, and cyclosporin A, a potent inhibitor of calcium release from mitochondria, prevented the AMA‐induced increases in [Ca^2+^]~i~. However, [Ca^2+^]~i~ increase by AMA was unaffected by dantrolene, which blocks the ryanodine receptor channel of the endoplasmic reticulum. BAPTA/AM (an intracellular Ca^2+^ chelator), dantrolene and cyclosporine A did not reverse the effect of AMA on ROS release. We also investigated whether intracellular calcium release inhibitor and antioxidant protect against AMA‐induced bone resorbing cytokine release. Trolox prevented the release of receptor activator of nuclear factor‐__κ__B ligand (RANKL), IL‐6, and TNF‐α induced by AMA. Moreover, the increased IL‐6 and TNF‐α release by AMA was markedly reduced by BAPTA/AM and cyclosporin A. However, BAPTA/AM did not reverse the effect of AMA on osteoprotegerin and RANKL. Taken together, these results demonstrate that mitochondrial ROS generation and Ca^2+^ influx by AMA is required for osteoblast death and bone resorbing cytokine release. Copyright © 2011 John Wiley & Sons, Ltd.