Lactobacillus plantarum 45 activates SHP2 through inhibition of oxidative stress to regulate osteoblast and osteoclast differentiation

Yaming Yang, Zheng Yan, Qinwen Xie, Yong Wang, Zhiying Liu, Min Lei
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Abstract

Background: The purpose of this study is to observe LP45 (Lactobacillus plantarum 45) to investigate the mechanism by which LP45 attenuates oxidative stress-induced damage and regulates the osteoblast-osteoclast balance. Materials and Methods: The oxidative stress level and osteoblast- and osteoclast-related proteins were detected by immunofluorescence staining, Western blotting, ROS fluorescent probe and ELISA. Osteoblast cell proliferation capacity was determined by the CCK-8 assay. X-ray observation and HE staining were used to detect the effect of LP45 on osteoporosis. Results: The expression level of SHP2 and Src was significantly increased, and the expression levels of NOX4, P22, P47, IL-1β, NLRP3, IRF3, RANK, β-catenin and INF-β were inhibited in LP45 group and LPS + LP45 group as compared to those in LPS group. Compared with that in LPS group, the concentration of SOD was increased and the concentration of MDA was decreased in LPS + LP45 group. The protein expressions of OPG, RANKL, RUNX3, RANK and β-catenin in LP45 group and LPS + LP45 group increased. The protein expressions of NF-κB, CREB and AP-1 in LP45 group and LPS + LP45 group decreased significantly. The results were also confirmed by immunofluorescence staining and ROS fluorescent probe. X-ray observation and HE staining showed that LP45 could inhibit the progression of osteoporosis. Conclusion: LP45 can exert its antioxidant effect by inhibiting the production of oxidative stress to activate the SHP2 signaling pathway, thus promoting osteoblast differentiation and repressing osteoclast formation to maintain bone homeostasis and improve bone metabolism.
植物乳杆菌 45 通过抑制氧化应激激活 SHP2,从而调节成骨细胞和破骨细胞分化
背景:本研究的目的是观察LP45(植物乳杆菌45),研究LP45减轻氧化应激引起的损伤和调节成骨细胞-破骨细胞平衡的机制。材料与方法:通过免疫荧光染色、Western印迹、ROS荧光探针和ELISA检测氧化应激水平、成骨细胞和破骨细胞相关蛋白。成骨细胞增殖能力通过 CCK-8 试验测定。用X射线观察和HE染色检测LP45对骨质疏松症的影响。结果LP45 组和 LPS + LP45 组与 LPS 组相比,SHP2 和 Src 的表达水平明显升高,NOX4、P22、P47、IL-1β、NLRP3、IRF3、RANK、β-catenin 和 INF-β 的表达水平受到抑制。与 LPS 组相比,LPS + LP45 组 SOD 浓度升高,MDA 浓度降低。LP45组和LPS + LP45组的OPG、RANKL、RUNX3、RANK和β-catenin的蛋白表达量增加。LP45 组和 LPS + LP45 组的 NF-κB、CREB 和 AP-1 蛋白表达量明显下降。免疫荧光染色和 ROS 荧光探针也证实了这一结果。X 射线观察和 HE 染色显示,LP45 可抑制骨质疏松症的进展。结论LP45可通过抑制氧化应激的产生来激活SHP2信号通路,从而发挥抗氧化作用,促进成骨细胞分化,抑制破骨细胞形成,维持骨平衡,改善骨代谢。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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