RRC ID 47958
著者 Hu J, Mao Z, He S, Zhan Y, Ning R, Liu W, Yan B, Yang J.
タイトル 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.
ジャーナル Biochem Pharmacol
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.
巻・号 136
ページ 109-121
公開日 2017-7-15
DOI 10.1016/j.bcp.2017.04.010
PII S0006-2952(17)30199-5
PMID 28408345
PMC PMC8316728
MeSH Animals Cell Line Dose-Response Relationship, Drug Drugs, Chinese Herbal / pharmacology Drugs, Chinese Herbal / therapeutic use Flavonoids / pharmacology Flavonoids / therapeutic use* Gene Expression Glucocorticoids / toxicity Glycogen Synthase Kinase 3 beta / biosynthesis* Humans Male Mice Mice, Inbred C57BL Osteoporosis / genetics Osteoporosis / metabolism* Osteoporosis / prevention & control Phosphatidylinositol 3-Kinases / biosynthesis* Tumor Suppressor Proteins / biosynthesis* Tumor Suppressor Proteins / genetics beta Catenin / biosynthesis*
IF 4.96
引用数 17
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
実験動物マウス RBRC04841