Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways.

Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways.
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芝麻素通过抑制破骨细胞生成和 RANKL 介导的 NF-kappa B 和 MAPK 信号通路来保护小鼠免受卵巢切除骨质流失

DOI:
10.3389/fphar.2021.664697
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发表时间:
2021
影响因子:
5.6
通讯作者:
Zhou B
Zhou B
中科院分区:
医学2区
文献类型:
--
作者:
Yang X;Liang J;Wang Z;Su Y;Zhan Y;Wu Z;Li J;Li X;Chen R;Zhao J;Xu J;Liu Q;Zhou B

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本文已提交给《药理学前沿》杂志的《实验药理学和药物发现》部分。绝经后骨质疏松症(PMOP)会增加骨折的风险,是女性最常见的骨病。 PMOP不仅增加死亡风险,还给无数家庭带来经济负担。目前,大多数用于治疗骨质疏松症的药物都有明显的副作用,因此寻找有效且无重大副作用的抗骨质疏松药物非常重要。芝麻素(Ses)是从芝麻油中提取的一种天然木脂素。许多研究表明Ses具有抗炎、抗氧化和抗癌作用,但它是否对骨质疏松症有作用尚不清楚。在本研究中,我们探讨了Ses在破骨细胞形成和骨吸收过程中的治疗作用,通过TRAcP染色和羟基磷灰石吸收测定发现Ses在体外有效抑制破骨细胞形成。通过对NF-κB通路、MAPK通路、c-Fos和NFATc1的Western blot分析发现,Ses不仅有效抑制RANKL诱导的NF-κB和MAPK信号通路的激活,而且显着降低了c-Fos和NFATc1的蛋白表达。通过qPCR测定了破骨细胞中特异表达的几个基因,Ses也被发现对这些基因的表达具有显着的抑制作用。此外,采用卵巢切除(OVX)小鼠诱导的骨质疏松模型来验证Ses可以有效减少体内雌激素缺乏引起的骨质流失。总之,Ses 显示出作为绝经后骨质疏松症新疗法的前景。
This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation in vitro through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency in vivo. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.
DOI: 10.1038/srep45964
发表时间: 2017-04-06
期刊: Scientific reports
影响因子: 4.6
作者:
Cong Q;Jia H;Li P;Qiu S;Yeh J;Wang Y;Zhang ZL;Ao J;Li B;Liu H
通讯作者: Liu H
DOI: 10.1084/jem.190.12.1741
发表时间: 1999-12-20
期刊: The Journal of experimental medicine
影响因子: --
作者:
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发表时间: 2018-03
期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子: --
作者:
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DOI: 10.1242/jcs.00082
发表时间: 2002-11-15
影响因子: 4
作者:
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通讯作者: Wagner, EF