成骨细胞中雌激素受体β介导雌激素对IL-6和TGF-β的调控作用

Regulation of interleukin-6 and transforming growth factor-β expressions by estrogen receptor β in osteoblast cell differentiation

[目的]利用小鼠胚胎成骨细胞前体细胞MC3T3-E1为细胞模型,研究雌激素与IL-6和TGF-β三者在成骨细胞分化中的具体作用机制,进一步在细胞水平探讨雌激素受体ERβ在雌激素功能中的作用。[方法]17β-雌二醇处理MC3T3-E1细胞后检测碱性磷酸酶活性、骨桥蛋白、骨保护素、骨钙素等成骨细胞相关因子的表达。同时17β-雌二醇处理后检测细胞因子IL-6和TGF-β的表达是否改变。然后分别用IL-6和TGF-β单独处理后检测MC3T3-E1细胞成骨分化相关因子和破骨细胞分化因子的表达。进一步利用siRNA干扰ERβ的表达,检测在17β-雌二醇诱导下IL-6和TGF-β表达的改变。[结果]雌激素能够诱导MC3T3-E1细胞碱性磷酸酶活性、骨桥蛋白、骨保护素、骨钙素的生成。雌激素处理后细胞因子IL-6的生成受到抑制,而TGF-β的表达上调。干扰了ERβ后,17β-雌二醇处理MC3T3-E1细胞后白细胞介素6及TGF-βmRNA的表达无明显改变。[结论]雌激素通过ERβ,调控IL-6和TGF-β的表达,进而调节成骨细胞的功能和骨的形成。

[Objective] This study aimed to investigate the roles of estrogen receptor β,interleukin 6（ IL- 6）,and transforming growth factor β（ TGF- β） in osteoblast differentiation in the mouse osteoblastic cell line MC3T3- E1. [Methods] The MC3T3- E1 cells were treated with different 17β- estradiol concentrations. Then,expressions of alkaline phosphatase activity,osteopontin,osteoprotegerin,and osteocalcin were detected,as well as those of TGF- β and IL- 6 in each 17β- estradiol- treated group. The MC3T3- E1 cells were treated with IL- 6 and TGF- β,respectively,and the aforementioned factors were also detected. Further use of small interfering RNA interfered with the estrogen receptor- β（ ERβ） expression and detected the IL- 6 and TGF- β expressions induced by 17β- estradiol. [Results] Estrogen induced the generation of alkaline phosphatase,osteocalcin,osteopontin,and osteoprotegerin in MC3T3- E1 cells. Inhibition of IL- 6 expression and upregulation of TGF- β expression were induced by estrogen. IL- 6 and TGF- β expressions had no obvious change by estradiol after the ER- β interference. [Conclusion] Estrogen regulates the IL- 6 and TGF- β expressions by ERβ,thereby regulating osteoblast function and bone formation.