Effects of dietary resveratrol on excess-iron-induced bone loss via antioxidative character

Estrogen deficiency has been considered to be a major cause of osteoporosis, but recent epidemiological evidence and mechanistic studies have indicated that aging and the associated increase in reactive oxygen species (ROS) are the proximal pathogenic factors. Through ROS-mediated reactions, iron can induce disequilibrium of oxidation and antioxidation and can cause bone loss in mice. Therefore, we investigated the effects of resveratrol (RES) on bone mineral density, bone microstructure and the osteoblast functions under iron-overload conditions. Excess iron disrupted the antioxidant/prooxidant equilibrium of the mice and induced the defect and the lesion of the bone trabecula as well as disequilibrium between bone formation and bone resorption in iron-overload mice. Oral administration of RES significantly prevented bone loss in the osteoporotic mice. RES reversed the reduction of Runx2, OCN and type I collagen from excess iron; up-regulated the level of FOXO1; and maintained the antioxidant/prooxidant equilibrium in the mice. RES also reduced the ratio of OPG/RANKL in MC3T3-E1 cells and in mice and significantly inhibited subsequent osteoclastogenesis. These results provide new insights into the antiosteoporosis mechanisms of RES through antioxidative effects, suggesting that RES can be considered a potential natural resource for developing medicines or dietary supplements to prevent and treat osteoporosis.