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植物雌激素通过抑制非经典雌激素受体,克服了双酚A对人永生化成骨细胞hFOB 1.19的不良影响。

Phytoestrogens by inhibiting the non-classical oestrogen receptor, overcome the adverse effect of bisphenol A on hFOB 1.19 cells.

作者信息

Thent Zar Chi, Froemming Gabriele Ruth Anisah, Ismail Aletza Binti Mohd, Fuad Syed Baharom Syed Ahmad, Muid Suhaila

机构信息

Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, 47000 Selangor, Malaysia.

Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak (UNIMAS), 94300 Kota Samarahan, Sarawak, Malaysia.

出版信息

Iran J Basic Med Sci. 2020 Sep;23(9):1155-1163. doi: 10.22038/ijbms.2020.45296.10545.

DOI:10.22038/ijbms.2020.45296.10545
PMID:32963737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7491500/
Abstract

OBJECTIVES

Since bisphenol A (BPA) induces bone loss and phytoestrogens enhance the osteoblastogenesis by binding to the non-classical and classical oestrogen receptors, respectively, the present study was aimed to observe the osteoprotective effect of phytoestrogens on BPA-induced osteoblasts in hFOB 1.19 cells.

MATERIALS AND METHODS

All groups of hFOB 1.19 cells were induced with 12.5 μg/ml of BPA except the control (Ctrl) group. Meanwhile, treated groups received phytoestrogens; Daidzein (Dz), Genistein (Gt), Equol (Eq) and 17β-oestradiol (Est) in different concentrations for 24 hr duration.

RESULTS

We found that the protein expression of non-classical oestrogen-related receptor (ERRG) was highly expressed in BPA group, whereas classical oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ) were relatively increased with phytoestrogens treatment under BPA exposure. The dense actin cytoskeletal filaments were also observed. qRT-PCR showed up-regulation of mitogen-activated protein kinase 3 (MAPK3) and G protein-coupled receptor 30 (GPR30) expressions; significant down-regulation of ERRG and up-regulation of ERα and ERβ were observed in phytoestrogens-treated cells, which was supported by the increased expressions of oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2).

CONCLUSION

Phytoestrogens improved the deteriorative effect of BPA via down-regulation of ERRG in hFOB 1.19 cells. This study showed that the efficacy of consumption of phytoestrogens in rendering them as potential therapeutic strategy in combating the adverse bone effects of BPA.

摘要

目的

由于双酚A(BPA)会导致骨质流失,而植物雌激素分别通过与非经典雌激素受体和经典雌激素受体结合来增强成骨细胞生成,因此本研究旨在观察植物雌激素对hFOB 1.19细胞中BPA诱导的成骨细胞的骨保护作用。

材料与方法

除对照组(Ctrl)外,所有hFOB 1.19细胞组均用12.5μg/ml的BPA诱导。同时,处理组接受不同浓度的植物雌激素;大豆苷元(Dz)、染料木黄酮(Gt)、雌马酚(Eq)和17β-雌二醇(Est),处理24小时。

结果

我们发现,非经典雌激素相关受体(ERRG)的蛋白表达在BPA组中高表达,而在BPA暴露下,植物雌激素处理后经典雌激素受体α(ERα)和雌激素受体β(ERβ)相对增加。还观察到密集的肌动蛋白细胞骨架丝。qRT-PCR显示丝裂原活化蛋白激酶3(MAPK3)和G蛋白偶联受体30(GPR30)表达上调;在植物雌激素处理的细胞中观察到ERRG显著下调,ERα和ERβ上调,雌激素受体1(ESR1)和雌激素受体2(ESR2)表达增加也支持了这一点。

结论

植物雌激素通过下调hFOB 1.19细胞中的ERRG改善了BPA的恶化作用。本研究表明,食用植物雌激素作为对抗BPA对骨骼不良影响的潜在治疗策略具有有效性。

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本文引用的文献

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Life Sci. 2018 Oct 1;210:214-223. doi: 10.1016/j.lfs.2018.08.057. Epub 2018 Aug 24.
2
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.大豆苷元通过雌激素受体依赖性的MEK/ERK和PI3K/Akt激活,刺激人成骨样MG-63细胞的成骨作用,促进其增殖、分化和抗凋亡。
Nutr Res. 2017 Jun;42:20-30. doi: 10.1016/j.nutres.2017.04.009. Epub 2017 May 6.
3
Daidzein increases OPG/RANKL ratio and suppresses IL-6 in MG-63 osteoblast cells.
大豆苷元可提高MG-63成骨细胞中骨保护素/核因子κB受体活化因子配体(OPG/RANKL)的比例,并抑制白细胞介素-6(IL-6)。
Int Immunopharmacol. 2016 Nov;40:32-40. doi: 10.1016/j.intimp.2016.08.014. Epub 2016 Aug 28.
4
Prunetin signals via G-protein-coupled receptor, GPR30(GPER1): Stimulation of adenylyl cyclase and cAMP-mediated activation of MAPK signaling induces Runx2 expression in osteoblasts to promote bone regeneration.染料木素通过G蛋白偶联受体GPR30(GPER1)发出信号:刺激腺苷酸环化酶和cAMP介导的MAPK信号激活可诱导成骨细胞中Runx2表达,从而促进骨再生。
J Nutr Biochem. 2015 Dec;26(12):1491-501. doi: 10.1016/j.jnutbio.2015.07.021. Epub 2015 Aug 8.
5
Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating d-Galactosamine induced fulminant hepatic failure in Wistar rats.染料木黄酮可调节核因子κB和丝裂原活化蛋白激酶(p - 38和细胞外信号调节激酶1/2)的表达,从而减轻d - 半乳糖胺诱导的Wistar大鼠暴发性肝衰竭。
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Br J Nutr. 2014 Jan 14;111(1):55-63. doi: 10.1017/S0007114513002043. Epub 2013 Jul 5.