Icariin Protects Against Glucocorticoid Induced Osteoporosis, Increases the Expression of the Bone Enhancer DEC1 and Modulates the PI3K/Akt/GSK3β/β-catenin Integrated Signaling Pathway

Overview

Journal Biochem Pharmacol

Specialties Biochemistry
Pharmacology

Date 2017 Apr 15

PMID 28408345

Citations 25

Authors

Jinhua Hu

Zhao Mao

Shuangcheng He

Yuanran Zhan

Rui Ning

Wei Liu

Bingfang Yan

Jian Yang

Affiliations

Soon will be listed here.

Abstract

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 DEC1, a structurally distinct helix-loop-helix protein. DEC1 overexpression promoted whereas DEC1 knockdown decreased osteogenic activity. Likewise, DEC1 overexpression and knockdown inversely regulated the expression of β-catenin and PIK3CA, an essential player in the Wnt/β-catenin and PI3K/Akt signaling pathways, respectively. Interestingly, DKK1, an inhibitor of Wnt/β-catenin signaling inhibitor, and LY294002, an inhibitor of PI3K/Akt signaling, abolished the induction of DEC1 by icariin. It is established that these two pathways are interconnected by the phosphorylation status of GSK3β. Dexamethasone decreased but icariin increased GSK3β phosphorylation. Finally, DEC1 deficient mice developed osteoporotic phenotypes. Taken together, it is concluded that DEC1 likely supports the action of icariin against glucocorticoid induced osteoporosis with an involvement of the PI3K/Akt/GSK3β/β-catenin integrated signaling pathway.

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