Jin Xin, Sun Jing, Yu Bo, Wang Yue, Sun Wei Jia, Yang Jing, Huang Su Hui, Xie Wen Li
Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin 300309, China; Department of Pharmacology, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, China.
Department of Pharmacology, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, China.
Nutr Res. 2017 Jun;42:20-30. doi: 10.1016/j.nutres.2017.04.009. Epub 2017 May 6.
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 17β-estradiol 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 ERα and ERβ, whereas the effects on cell proliferation are primarily mediated by ERα. However, the effects of 17β-estradiol on osteoblastic proliferation and survival are mediated by both ER isotypes, and the effects on osteoblastic differentiation are primarily mediated by ERα. The use of specific inhibitors indicated that activation of the mitogen-activated 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.
大豆苷元是一种天然的大豆异黄酮，其结构与雌二醇相似，对骨质疏松症具有保骨作用。然而，成骨的分子机制仍不清楚。我们假设大豆苷元通过雌激素受体（ER）依赖性信号通路刺激成骨。为了验证这一假设，我们研究了大豆苷元与17β-雌二醇相比，对含有两种ER亚型的人成骨样MG-63细胞增殖、分化和顺铂诱导凋亡的影响。结果表明，大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的表达减少细胞凋亡。大豆苷元的上述作用可被ER拮抗剂ICI 182780共同处理所阻断。使用小干扰RNA技术，我们进一步证明，大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由ERα和ERβ共同介导，而对细胞增殖的影响主要由ERα介导。然而，17β-雌二醇对成骨细胞增殖和存活的影响由两种ER亚型共同介导，对成骨细胞分化的影响主要由ERα介导。使用特异性抑制剂表明，丝裂原活化蛋白激酶激酶/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。
