Daidzein stimulates osteogenesis facilitating proliferation, differentiation, and antiapoptosis in human osteoblast-like MG-63 cells via estrogen receptor-dependent MEK/ERK and PI3K/Akt activation
Daidzein stimulates osteogenesis facilitating proliferation, differentiation, and antiapoptosis in human osteoblast-like MG-63 cells via estrogen receptor-dependent MEK/ERK and PI3K/Akt activation
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大豆黄酮通过雌激素受体依赖性 MEK/ERK 和 PI3K/Akt 激活刺激成骨，促进人成骨样 MG-63 细胞的增殖、分化和抗凋亡
DOI：
10.1016/j.nutres.2017.04.009
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发表时间：
2017-06-01
影响因子：
4.5
通讯作者：
Xie, Wen Li
中科院分区：
文献类型：
--
作者：
Jin, Xin;Sun, Jing;Xie, Wen Li
大豆黄酮是一种天然大豆异黄酮，其结构与雌二醇相似，具有抗骨质疏松症的骨保护作用。然而，成骨的分子机制仍不清楚。我们假设大豆黄酮通过雌激素受体（ER）依赖性信号通路刺激成骨。为了检验这一假设，我们研究了黄豆苷元与 17β-雌二醇对含有 2 种 ER 亚型的人成骨细胞样 MG-63 细胞的增殖、分化和顺铂诱导的细胞凋亡的影响。结果表明，黄豆苷元通过改变细胞周期分布刺激细胞增殖，通过增加碱性磷酸酶活性和胶原蛋白含量促进细胞分化，并通过上调Bcl-xL表达减少相关细胞凋亡。通过与ER拮抗剂ICI 182780共处理，可以阻止黄豆苷元的上述作用。利用小干扰RNA技术，我们进一步证明黄豆苷元对碱性磷酸酶活性、胶原蛋白含量和细胞凋亡的影响是由ER α和ER β介导的，而对细胞增殖的影响主要是由ER α介导的。然而，17β-雌二醇对成骨细胞增殖和存活的影响是由两种ER同种型介导的，而对成骨细胞分化的影响主要是由ERα介导的。特定抑制剂的使用表明，丝裂原激活蛋白激酶激酶/细胞外调节激酶 (MEK/ERK) 和磷酸肌醇 3-激酶/蛋白激酶 B 或 PKB (PI3K/Akt) 信号通路的激活至少部分解释了大豆苷元的这些作用。综上所述，结果表明，大豆苷元通过以 ER 依赖性方式激活 MEK/ERK 和 PI3K/Akt，促进人成骨样 MG-63 细胞的增殖、分化和抗凋亡，从而刺激成骨。 (C) 2017 Elsevier Inc. 保留所有权利。
Daidzein, a natural soy isoflavone, has a structure similar to estradiol and exhibiting bone-sparing effects against osteoporosis. However, the molecular mechanisms of osteogenesis remain unclear. We hypothesized that daidzein stimulates osteogenesis through estrogen receptor (ER) dependent signal pathways. To test this hypothesis, we investigated the effects of daidzein compared with 17 beta-estadiol on proliferation, differentiation, and cisplatin-induced apoptosis in human osteoblast-like MG-63 cells containing 2 ER isoforms. The results showed that daidzein stimulated cell proliferation by altering cell cycle distribution, promoted cell differentiation by increasing the alkaline phosphatase activity and collagen content, and reduced cell apoptosis associated by up-regulating the expression of Bcl-xL. The above actions of daidzein were prevented by cotreatment with the ER antagonist ICI 182780. Using small interfering RNA technology, we further demonstrated that the effects of daidzein on alkaline phosphatase activity, collagen content, and cell apoptosis are mediated by both ER alpha and ER beta, whereas the effects on cell proliferation are primarily mediated by ER alpha. However, the effects of 17 beta-estradiol on osteoblastic proliferation and survival are mediated by both ER isotypes, and the effects on osteoblastic differentiation are primarily mediated by ER alpha. The use of specific inhibitors indicated that activation of the mitogenactivated protein kinase kinase/extracellular regulated kinase (MEK/ERK) and phosphoinositide 3-kinase/protein kinase B or PKB (PI3K/Akt) signaling pathway at least partially accounts for these effects of daidzein. Taken together, the results indicate that daidzein stimulates osteogenesis through facilitating proliferation, differentiation, and antiapoptosis in human osteoblast-like MG-63 cells via activation of MEK/ERK and PI3K/Akt in an ER-dependent manner. (C) 2017 Elsevier Inc. All rights reserved.