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.
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.
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淫羊藿苷可防止糖皮质激素诱导的骨质疏松症，增加骨增强剂 DEC1 的表达并调节 PI3K/Akt/GSK3β/β-连环蛋白整合信号通路。
DOI：
10.1016/j.bcp.2017.04.010
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发表时间：
2017-07-15
影响因子：
5.8
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Hu J;Mao Z;He S;Zhan Y;Ning R;Liu W;Yan B;Yang J
骨质疏松症是一个严重的全球公共卫生问题。几个世纪甚至几千年来，淫羊藿一直被用来治疗风湿病。淫羊藿苷是淫羊藿的主要活性成分之一，是一种黄酮醇苷。在这项研究中，我们已经表明，淫羊藿苷对糖皮质激素诱导的SaoS-2细胞和小鼠的神经病变的变化。我们还表明，地塞米松（糖皮质激素）抑制和淫羊藿苷诱导DEC 1，一种结构独特的螺旋-环-螺旋蛋白。DEC 1过表达促进成骨活性，而DEC 1敲低则降低成骨活性。同样地，DEC 1过表达和敲低分别反向调节β-连环蛋白和PIK 3CA的表达，它们分别是Wnt/β-连环蛋白和PI 3 K/Akt信号通路中的重要参与者。有趣的是，Wnt/β-catenin信号通路抑制剂DKK 1和PI 3 K/Akt信号通路抑制剂LY 294002可阻断淫羊藿苷对DEC 1的诱导作用。已确定这两种途径通过GSK 3 β的磷酸化状态相互关联。地塞米松降低GSK 3 β磷酸化水平，而淫羊藿苷增加GSK 3 β磷酸化水平。最后，DEC 1缺陷型小鼠发展出了类风湿性关节炎表型。综上所述，可以得出结论，DEC 1可能支持淫羊藿苷对抗糖皮质激素诱导的骨质疏松症的作用，并参与PI 3 K/Akt/GSK 3 β/β-catenin整合信号通路。
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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影响因子：
1.7
作者：
Jiang, Fang;Wang, Xin-Luan;Yao, Xin-Sheng
通讯作者：
Yao, Xin-Sheng
影响因子：
4.8
作者：
Li, YX;Xie, MX;Yan, BF
通讯作者：
Yan, BF
DOI：
10.1016/j.bbrc.2015.02.161
发表时间：
2015-05-01
影响因子：
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作者：
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通讯作者：
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影响因子：
6.6
作者：
Iwata, Tomoyuki;Kawamoto, Takeshi;Kato, Yukio
通讯作者：
Kato, Yukio
影响因子：
5.6
作者：
Hovhannisyan, Hayk;Zhang, Ying;Hassan, Mohammad Q.;Wu, Hai;Glackin, Carlotta;Lian, Jane B.;Stein, Janet L.;Montecino, Martin;Stein, Gary S.;van Wijnen, Andre J.
通讯作者：
van Wijnen, Andre J.