Conclusions
These results demonstrated that CUR was able to alleviate bone loss induced by oxidative stress resulting from iron overload, suggesting its potential use for the treatment of primary osteoporosis and bone loss in iron-overload-related diseases.
Methods
An iron-overload mice model was used to study the protective effects of CUR on bone loss induced by oxidative stress. Serum bone metabolism markers and antioxidant enzymes were also measured. To explore the antioxidant mechanism of CUR, the MC3T3-E1 osteoblastic cell line was used.
Results
In vivo studies showed that BMD and microarchitectural parameters were improved after a 3-month administration of CUR. CUR improved the biochemical parameters related to bone metabolism and the expressions of Runx2, OCN, and type 1 collagen and increased the formation of bone-mineralized nodules in vitro. CUR also inhibited ROS generation and increased the activities of antioxidant enzymes both in vivo and in vitro treated with excess iron. CUR can upregulate the level of FoxO1 and Nrf2, downregulate the level of p53 and the phosphorylation level of FoxO1, improve nuclear translocation of FoxO1, probably by inhibiting the IGFR/AKT signaling pathway, then increased cell viability and autophagy, and reduced apoptosis of MC3T3-E1 cells treated with excess iron by regulating the expression of FoxO1 target genes MnSOD, Gadd45a, Bim, FasL, and Rab7. Conclusions: These results demonstrated that CUR was able to alleviate bone loss induced by oxidative stress resulting from iron overload, suggesting its potential use for the treatment of primary osteoporosis and bone loss in iron-overload-related diseases.