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淫羊藿黄酮通过雌激素受体途径刺激原代间充质干细胞的成骨分化并抑制其成脂分化。

Flavonoids of Herba Epimedii stimulate osteogenic differentiation and suppress adipogenic differentiation of primary mesenchymal stem cells via estrogen receptor pathway.

作者信息

Zhang Dawei, Liu Li, Jia Zhenbin, Yao Xinsheng, Yang Mengsu

机构信息

a School of Pharmacy, Guangdong Medical University , Dongguan , PR China .

b Guangdong Key Laboratory for Research and Development of Natural Drugs , Guangdong Medical College , Zhanjiang , PR China .

出版信息

Pharm Biol. 2016;54(6):954-63. doi: 10.3109/13880209.2015.1079224. Epub 2015 Oct 9.

Abstract

CONTEXT

Accumulating evidence indicates that Herba Epimedii [Epimedii folium (Berberidaceae)] has anti-osteoporotic effect by stimulating osteoblastic bone formation and reducing osteoclastic bone resorption. However, the effect of Herba Epimedii in regulating the cross-talk between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) remains unclear.

OBJECTIVE

The present study investigates the effect of total flavonoids of Herba Epimedii (HETF) on the osteogenesis and adipogenesis of primary MSCs.

MATERIALS AND METHODS

HETF were prepared and identified by HPLC-fingerprinting, primary mouse MSCs in the presence of 0.006-6 μg/mL HETF for 2-10 d were subject to morphological, biochemical, and quantitative real-time PCR analysis.

RESULTS

Sixteen chemical components were identified in HETF by HPLC-fingerprinting and account for over 95% of the total area of HPLC peaks. During osteogenesis of MSCs, 0.006-6 μg/mL HETF promoted the proliferation of MSCs from 17% to 22%, increased alkaline phosphatase activity up to 3.7-fold (0.6 μg/mL), and extracellular calcium deposits from 1.2- to 1.4-folds by up-regulating the expression of runt-related transcription factor-2 (Runx-2) and bone morphogenetic protein-2 (BMP-2). Meanwhile, HETF suppressed the adipogenesis of MSCs by reducing the formation of adipocyte-like cells and accumulation of fat droplets by down-regulating the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ). The above biological activities of HETF were mainly through estrogen receptor-mediated pathway, which were blocked by estrogen receptor antagonist, ICI 182,780.

CONCLUSION

HETF could regulate Runx-2-mediated osteogenesis and PPAR-γ-mediated adipogenesis in MSCs and thus exhibit beneficial effects to bone health, which suggests a new strategy for treating patients with osteoporosis and obesity.

摘要

背景

越来越多的证据表明,淫羊藿[淫羊藿叶(小檗科)]通过刺激成骨细胞骨形成和减少破骨细胞骨吸收具有抗骨质疏松作用。然而,淫羊藿在调节间充质干细胞(MSC)成骨与成脂分化之间的相互作用方面的作用仍不清楚。

目的

本研究探讨淫羊藿总黄酮(HETF)对原代MSC成骨和成脂的影响。

材料与方法

制备HETF并通过HPLC指纹图谱进行鉴定,将原代小鼠MSC在0.006 - 6μg/mL HETF存在下培养2 - 10天,进行形态学、生化和定量实时PCR分析。

结果

通过HPLC指纹图谱在HETF中鉴定出16种化学成分,占HPLC峰总面积的95%以上。在MSC成骨过程中,0.006 - 6μg/mL HETF使MSC的增殖从17%提高到22%,碱性磷酸酶活性提高至3.7倍(0.6μg/mL),细胞外钙沉积提高1.2 - 1.4倍,这是通过上调 runt相关转录因子2(Runx - 2)和骨形态发生蛋白2(BMP - 2)的表达实现的。同时,HETF通过下调过氧化物酶体增殖物激活受体γ(PPAR - γ)的表达,减少脂肪细胞样细胞的形成和脂滴积累,从而抑制MSC的成脂。HETF的上述生物学活性主要通过雌激素受体介导的途径,雌激素受体拮抗剂ICI 182,780可阻断该途径。

结论

HETF可调节MSC中Runx - 2介导的成骨和PPAR - γ介导的成脂,从而对骨骼健康产生有益影响,这为治疗骨质疏松症和肥胖症患者提供了一种新策略。

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