补肾健骨汤通过体外抑制MMP2表达和激活MAPK通路缓解骨质疏松症

IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Pengyuan Chen, Jiong Lin
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引用次数: 0

摘要

目的探讨BJD抗骨质疏松的确切机制。方法利用高效液相色谱法,从公共数据库中筛选BJD的有效成分和药物靶点。获得了与骨质疏松相关的差异表达基因,随后通过PPI网络确定了BJD和骨质疏松的重叠靶点。通过分子对接实验和分子动力学模拟验证了活性化合物与枢纽靶点之间的结合作用。通过体外实验验证BJD抗骨质疏松的作用和机制。结果分离得到3个核心活性化合物。分子对接显示了这三个化合物对PTGS2、MMP2和ADORA2B的亲和力。在lps诱导的MC3T3-E1成骨细胞中,BJD显著提高了细胞活力,恢复了ALP活性。在lps诱导的成骨细胞中,BJD降低了MMP2和PTGS2的表达,而升高了ADORA2B的表达。BJD可能通过减轻MAPK信号的激活来缓解骨质疏松症。MMP2水平升高使MC3T3-E1细胞迁移能力受损,BJD处理后lps诱导的MC3T3-E1细胞ALP、COLI、OCN、OPN表达水平显著升高,成骨钙结节形成不完全,沉积不完整。结论bjd通过抑制MMP2的表达和激活MAPK信号通路来缓解骨质疏松症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bushen Jiangu decoction alleviates osteoporosis by inhibiting MMP2 expression and activation of the MAPK pathway in vitro

Objectives

To explore the precise mechanism of BJD against osteoporosis.

Methods

The active compounds and drug targets of BJD were screened from public databases and identified by HPLC. Differentially expressed genes related to osteoporosis were obtained, followed by overlapping targets of BJD and osteoporosis identified by PPI networks. Then the binding interactions between active compounds and hub targets were validated by molecular docking vina followed by molecular dynamics simulations. The effects and mechanisms of BJD against osteoporosis was validated through in vitro experiments.

Results

Three core active compounds in BJD were obtained. Molecular docking highlighted the affinity of the three compounds towards PTGS2, MMP2, and ADORA2B. In the LPS-induced MC3T3-E1 osteoblast cells, BJD significantly promoted cell viability and revived ALP activity. BJD reduced the expression of MMP2 and PTGS2 whereas elevated ADORA2B expression in the LPS-induced osteoblasts. BJD could alleviate osteoporosis by alleviating the activation of the MAPK signaling. Elevated levels of MMP2 impaired the migration capacity, and significantly increased ALP, COLI, OCN and OPN expression levels in LPS-induced MC3T3-E1 cells after BJD treatment, as well as the osteoblast calcium nodules were incompletely formed and deposited.

Conclusion

BJD alleviated osteoporosis by inhibiting MMP2 expression and activation of MAPK signaling.
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来源期刊
Tissue & cell
Tissue & cell 医学-解剖学与形态学
CiteScore
3.90
自引率
0.00%
发文量
234
期刊介绍: Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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