Abstract
Reactive oxygen species (ROS) level is reported to increase in early stage of RANKL-induced osteoclast differentiation. The purpose of this study is to investigate the suppressive effect of carnosic acid (CA) by regulation of ROS during RANKL-induced osteoclast differentiation. The potent inhibitory effect of CA on RANKL-induced osteoclast differentiation was observed using TRAP staining and multi-nuclear osteoclast cell counting assay. The suppressive effect of CA on the production of ROS and superoxide anion dose-dependently increased between 1 μM and 20 μM. CA attenuated the translocation of Nox1 activating factor, p47phox, to the membrane leading to the decrease of ROS generation. In addition, CA activated Nrf2 and its transcriptional targets and scavenged RANKL-induced ROS contributing to the decrease of ROS level. These results indicate that CA can inhibit RANKL-induced osteoclastogenesis through the down-regulation of ROS generation and the up-regulation of ROS scavenging.
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