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Zingerone Promotes Osteoblast Differentiation Via MiR-200c-3p/smad7 Regulatory Axis in Human Bone Mesenchymal Stem Cells.
Zingerone 通过 MiR-200c-3p/smad7 调控轴促进人骨髓间充质干细胞向成骨细胞分化
- 影响因子:2.03
- DOI:10.12659/MSM.919309
- 作者列表:"Song Y","Mou R","Li Y","Yang T
- 发表时间:2020-03-08
Abstract
:BACKGROUND Osteoblast differentiation is a critical process to maintain the stability of the bone homeostasis. Zingerone, 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (ZG), isolated from ginger, performs a wide range of biological functions in human diseases. The objective of this paper was to clarify the role of ZG in human bone mesenchymal stem cells (hBMSCs) and associated mechanisms of ZG promoting osteoblast differentiation. MATERIAL AND METHODS The cytotoxicity of ZG was detected by MTT assay. The expression levels of miR-200c-3p, smad7, and osteoblast differentiation markers (alkaline phosphatase [ALP], osteocalcin [OC], osterix [OSX] and runt-related transcription factor 2 [RUNX2]) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of smad7, ALP, OC, OSX, and RUNX2 were quantified by western blot analysis. The target mRNAs were predicted by bioinformatics tools TargetScan. The interaction between miR-200c-3p and smad7 was verified by luciferase reporter assay and RIP assay. RESULTS ZG was nontoxic to hBMSCs, and it accelerated osteoblast differentiation by inducing the expression of ALP, OC, OSX, and RUNX2. MiR-200c-3p was upregulated, but smad7 was downregulated in hBMSCs treated with ZG at different concentrations at different periods. Besides, miR-200c-3p positively regulated the expression of ALP, OC, OSX, and RUNX2 in ZG-induced hBMSCs. Moreover, miR-200c-3p targeted smad7 and strengthened the expression of ALP, OC, OSX, and RUNX2 in ZG-induced hBMSCs by downregulating smad7. CONCLUSIONS ZG contributed to osteoblast differentiation via miR-200c-3p/smad7 regulatory axis by promoting the expression of ALP, OC, OSX, and RUNX2 in hBMSCs.
摘要
背景: 成骨细胞分化是维持骨稳态稳定的关键过程。从生姜中分离得到的姜酮,4-(4-羟基-3-甲氧基苯基)-2-丁酮 (ZG),在人类疾病中具有广泛的生物学功能。本文旨在阐明 ZG 在人骨髓间充质干细胞 (hBMSCs) 中的作用及 ZG 促进成骨细胞分化的相关机制。材料与方法采用 MTT 法检测 ZG 的细胞毒性。MiR-200c-3p 、 smad7 和成骨细胞分化标志物 (碱性磷酸酶 [ALP] 、骨钙素 [OC] 、 osterix [OSX] 和 runt 相关转录因子 2 [RUNX2]) 的表达水平通过定量实时聚合酶链反应 (qRT-PCR) 进行评估。通过 western blot 分析定量 smad7 、 ALP 、 OC 、 OSX 和 RUNX2 的蛋白水平。通过生物信息学工具 TargetScan 预测靶 mrna。通过荧光素酶报告基因实验和 RIP 实验验证了 miR-200c-3p 与 smad7 的相互作用。结果 ZG 对 hBMSCs 无毒,通过诱导 ALP 、 OC 、 OSX 和 runx2 的表达加速成骨细胞分化。在不同浓度 ZG 处理的 hBMSCs 中,MiR-200c-3p 上调,而 smad7 下调。此外,miR-200c-3p 对 ZG 诱导的 hBMSCs 中 ALP 、 OC 、 OSX 和 RUNX2 的表达具有正向调节作用。此外,miR-200c-3p 靶向 smad7,并通过下调 smad7 加强 ZG 诱导的 hBMSCs 中 ALP 、 OC 、 OSX 和 RUNX2 的表达。结论 ZG 通过促进 hBMSCs ALP 、 OC 、 OSX 和 RUNX2 的表达,通过 miR-200c-3p/smad7 调控轴促进成骨细胞分化。
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