Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production.
The bone protective effects of resveratrol have been demonstrated in several osteoporosis models while the underlying mechanism is largely unclear. In the present study, we evaluated the effects of resveratrol on differentiation and apoptosis of murine osteoclast progenitor RAW 264.7 cells. We found that resveratrol at non-toxic concentrations dose-dependently inhibited RANKL-induced osteoclast differentiation and induced apoptosis. Resveratrol has been shown to be an activator of Sirt1, a NAD(+) dependent protein deacetylase, and has been demonstrated to mimic estrogen. However, we found that although Sirt1 protein was abundantly expressed in RAW264.7 cells, the specific Sirt1 inhibitor EX-527 could not attenuate the inhibition of osteoclastogenesis mediated by resveratrol. Also, the effects of resveratrol could not be attenuated by ICI-182780, a high affinity estrogen receptor antagonist. The central role of reactive oxygen species (ROS) in RANKL-induced osteoclast differentiation has recently been clarified. We found that resveratrol suppressed RANKL-induced ROS generation in a concentration dependent manner. We postulate that the direct inhibitory effects of resveratrol on osteoclastogenesis are mediated via inhibition of ROS generation.
He
Xu
X
Department for Clinical Science, Intervention and Technology, Division of Orthopedics, Karolinska Institutet, Stockholm, Sweden.
Andersson
Göran
G
Lindgren
Urban
U
Li
Yan
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013267:Stilbenes / Q000494:pharmacology*
C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D000975:Antioxidants; D002227:Carbazoles; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D013267:Stilbenes; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol