Glycyrrhizin improves bone metabolism in ovariectomized mice via inactivating NF-kappa B signaling
Glycyrrhizin improves bone metabolism in ovariectomized mice via inactivating NF-kappa B signaling
复制标题
甘草甜素通过灭活 NF-κ B 信号改善卵巢切除小鼠的骨代谢
DOI：
10.1080/13697137.2020.1828853
复制
发表时间：
2021
期刊：
影响因子：
2.8
通讯作者：
Wang J. R.
中科院分区：
文献类型：
--
作者：
Tang Y.;Lv X. L.;Bao Y. Z.;Wang J. R.
绝经后骨质疏松症（Postmenopausal osteoporosis，PMO）是一种常见的代谢性骨病，发病率高，并发症严重.在这里，我们研究了骨代谢的影响，使用卵巢切除（OVX）小鼠model.MethodsOsteoclast-related基因的表达和成骨细胞的功能进行了评估，在RAW264.7细胞和骨髓来源的单核细胞（BBM）通过实时聚合酶链反应和骨吸收测定。对于动物研究，将雌性C57 BL/6 J小鼠随机分为假手术组、OVX组和OVX + Ehrin组。通过显微计算机断层扫描、双能X线吸收测定法和组织形态计量学分析骨量和骨小梁微结构。采用抗酒石酸酸性磷酸酶染色法和Western blotting法分别研究了核因子-κB受体激活剂（NF-κB）配体诱导破骨细胞的生成和NF-κB信号通路。此外，当在有骨钙素存在的情况下孵育骨钙素时，形成较少的骨吸收陷窝。甘草甜素改善OVX小鼠骨丢失和骨小梁参数。从OVX小鼠中分离的BclA显示出更高的RANKL诱导破骨细胞生成的能力，这被BclA极大地逆转。OVX小鼠BMPs中IκB-α和NF-κB-p65的Ser 32和Ser 536磷酸化水平显著升高，c-FOS和NFATc-1蛋白水平显著升高，这些均被BMPs抑制。
ObjectivesPostmenopausal osteoporosis (PMO) is a prevalent metabolic bone disease with high morbidity and serious complications. Here, we studied the effect of glycyrrhizin on bone metabolism using the ovariectomized (OVX) mouse model.MethodsOsteoclast-related gene expression and osteoclastic function were evaluated in RAW264.7 cells and bone marrow-derived monocytes (BMMs) by real-time polymerase chain reaction and bone resorption assay. For animal studies, female C57BL/6J mice were randomly divided into sham operated, OVX and OVX with glycyrrhizin groups. Bone mass and trabecular microarchitecture were analyzed by micro-computed tomography, dual X-ray absorptiometry, and histomorphometric analysis. Receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclastogenesis and the NF-κB signaling pathway were studied by tartrate-resistant acid phosphatase staining and western blotting, respectively.ResultsGlycyrrhizin inhibits RANKL-induced expression ofNfatc-1,c-Fos,Trap,Ds-stamp, andCtskin RAW264.7 cells. Also, fewer bone resorption pits form when BMMs are incubated in the presence of glycyrrhizin. Glycyrrhizin ameliorates bone loss and improves trabecular bone parameters in OVX mice. BMMs isolated from OVX mice show higher ability of RANKL-induced osteoclastogenesis, which is tremendously reversed by glycyrrhizin. There is significantly higher phosphorylation of IκB-α at Ser32 and NF-κB p65 at Ser536, as well as increased protein levels of c-FOS and NFATc-1 in BMMs of OVX mice, which are all greatly suppressed by glycyrrhizin.ConclusionsOur findings imply that glycyrrhizin is a potential efficient adjuvant therapeutic for PMO.