Icariin protects against glucocorticoid induced osteoporosis, increases the expression of the bone enhancer DEC1 and modulates the PI3K/Akt/GSKβ/β-catenin integrated signaling pathway

Osteoporosis is a serious public health concern worldwide. Herba epimedii has been used for centuries and even thousands of years to treat osteoporotic conditions. Icariin, a flavonol glycoside, is one of the major active ingredients. In this study, we have shown that icariin protected against glucocorticoid-induced osteoporotic changes in SaoS-2 cells and mice. We have also shown that dexamethasone (a glucocorticoid) suppressed and icariin induced DECI, a structurally distinct helix-loop-helix protein. DECI overexpression promoted whereas DECI knockdown decreased osteogenic activity. Likewise, DEC1 over expression and knockdown inversely regulated the expression of beta-catenin and PIK3CA, an essential player in the Wnt/beta-catenin and PI3K/Akt signaling pathways, respectively. Interestingly, DKK1, an inhibitor of Wnt/beta-catenin signaling inhibitor, and LY294002, an inhibitor of PI3K/Akt signaling, abolished the induction of DECI by icariin. It is established that these two pathways are interconnected by the phosphorylation status of GSK3 beta. Dexamethasone decreased but icariin increased GSK3 beta phosphorylation. Finally, DECI deficient mice developed osteoporotic phenotypes. Taken together, it is concluded that DECI likely supports the action of icariin against glucocorticoid induced osteoporosis with an involvement of the PI3K/Akt/GSK3 beta/beta-catertin integrated signaling pathway. (C) 2017 Elsevier Inc. All rights reserved.