Equol exerts a protective effect on postmenopausal osteoporosis by upregulating OPG/RANKL pathway
Equol exerts a protective effect on postmenopausal osteoporosis by upregulating OPG/RANKL pathway
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DOI：
10.1016/j.phymed.2022.154509
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发表时间：
2022-10-23
期刊：
影响因子：
7.9
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Ni, Xiangmin;Wu, Bin;Wang, Jian
背景：雌激素缺乏是绝经后骨质疏松症（PMOP）的主要原因，植物雌激素大豆异黄酮（SI）已被证明可以改善PMOP。雌马酚（Equol，Eq）是植物雌激素大豆异黄酮（SI）的体内代谢产物，具有比其母体化合物更稳定的结构和更强的生物活性，具有最大的雌激素活性。目的：探讨Eq对POMP的治疗作用及其机制。方法：体外培养人成骨样细胞ROS 1728，分别加入不同剂量的Eq、雌二醇（E2）。采用CCK-8和流式细胞仪检测Eq对成骨细胞增殖、凋亡、细胞周期的影响，采用实时定量PCR（qRT-PCR）和Western blot（WB）检测成骨细胞OPG/RANK/RANKL信号通路的表达，并采用RNA沉默技术探讨Eq发挥作用的受体。结果：Eq能促进成骨细胞增殖，抑制成骨细胞凋亡，增加S期和G2/M期成骨细胞比例，并呈剂量依赖性。在机制上，Eq处理上调成骨细胞中OPG和OPG/RANKL比率的表达，并且这种调节作用主要通过ER β受体介导。在体研究中，Eq改善了PMOP大鼠模型股骨的微观结构和BMD，这与E2的骨保护作用相似。Eq或E2治疗组血清Ca、1，25（OH）2D 3、骨钙素（BGP）和I型前胶原（PC 1）水平升高，血清磷（P）、甲状旁腺激素（PTH）、吡啶醇（PYD）、抗酒石酸酸性磷酸酶（TRAP）和尿脱氧吡啶啉（DPD）水平降低。结论：Eq可通过联合收割机与ER β结合，上调OPG/RANKL信号通路，对PMOP发挥保护作用。
Backgroud: Estrogen deficiency is the leading cause of postmenopausal osteoporosis(PMOP) and phytoestrogens soy isoflavones (SI) have been shown to improve PMOP. Equol (Eq), an in vivo metabolite of phytoestrogens soy isoflavones (SI), has a more stable structure and stronger biological activity than its parent compound and has the greatest estrogenic activity. However, there are few studies on the therapeutic effect of Eq on PMOP.Purpose: To explore the therapeutic effect and mechanisms of Eq on POMP.Methods: Osteoblast-like cells ROS1728 were cultured with different doses of Eq, estradiol (E2), separately. The effect of Eq on the proliferation, apoptosis, cell cycle of osteoblasts were detected by CCK-8 and flow cytometry, and the expression of OPG/RANK/RANKL signaling pathway of osteoblasts was detected by Quantitative real-time PCR (qRT-PCR) and Western blot (WB), and RNA silencing technology were carried out to explore the receptors through which Eq plays a role. Then PMOP rat model was established and treated by Eq or E2 to further verification of the effect and mechanism of Eq on PMOP.Result: Eq promoted the proliferation and inhibited the apoptosis of osteoblasts and increased the proportion of osteoblasts in the S phase and G2/M phase in a dose-dependent manner. Mechanistically, Eq treatment upregulated the expression of OPG and OPG/RANKL ratio in osteoblasts and this regulatory effect was mainly mediated through the ER beta receptor. Furthermore, in vivo study, Eq improved microstructure and BMD of the femur of PMOP rat model, which imitated the osteoprotective effect of E2. Moreover, the Eq or E2 treatment increased serum levels of Ca, 1,25(OH)2D3, bone Gla-protein(BGP), and Type I procollagen (PC1), and reduced serum levels of phosphorus (P), parathyroid hormone(PTH), pyridinol (PYD), tartrate-resistant acid phosphatase (TRAP) and urinary level of deoxypyridinoline (DPD) in the treatment OVX group compared with the untreated OVX group. Meanwhile, Eq or E2 markedly induced the mRNA and protein expression of OPG and OPG/RANKL ratio.Conclusion: Eq can combine with ER beta and exert a protective effect on PMOP by upregulating OPG/RANKL pathway.