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白藜芦醇通过 miR-193a/SIRT7 轴促进骨髓间充质干细胞的成骨分化。

Resveratrol Promotes Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Through miR-193a/SIRT7 Axis.

机构信息

Department of Orthopedic, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Gulou District, Fuzhou, 350001, Fujian Province, China.

出版信息

Calcif Tissue Int. 2022 Jan;110(1):117-130. doi: 10.1007/s00223-021-00892-7. Epub 2021 Sep 3.

Abstract

Resveratrol (RES) is a novel dietary phenol compound derived from plants and has been studied extensively for its health benefit and medical potential including osteoporosis. The purpose of this study is to investigate the role of resveratrol in osteoporosis in vivo and in vitro and explore the mechanism of osteogenic differentiation of BMSCs. RT-qPCR, ELISA, and Western blot were used to measure the expression level of miR-193a, SIRT7, and osteogenic markers proteins. The interaction between miR-193a and SIRT7 was validated by dual-luciferase reporter assay. Moreover, MTT assay was conducted to detect cell viability. Alizarin red s staining was used to examine bone formation and calcium deposits. The ovariectomized rat model was set up successfully and HE staining was used to examine femoral trabeculae tissue. Our results showed that miR-193a was overexpressed, while SIRT7 was downregulated in osteoporosis. RES suppressed miR-193a to promote osteogenic differentiation. Mechanically, miR-193a targeted and negative regulated SIRT7. Additionally, it was confirmed that SIRT7 promoted osteogenic differentiation of BMSCs through NF-κB signaling pathway. Further study indicated that RES exerted its beneficial function through miR-193a/SIRT7-mediated NF-κB signaling to alleviate osteoporosis in vivo. Our research suggested that the RES-modulated miR-193a inhibition is responsible for the activation of SIRT7/NF-κB signaling pathway in the process of osteogenic differentiation, providing a novel insight into diagnosis and treatment of osteoporosis.

摘要

白藜芦醇(RES)是一种新型植物来源的膳食酚类化合物,因其具有健康益处和医学潜力,包括骨质疏松症,已被广泛研究。本研究旨在探讨白藜芦醇在体内和体外骨质疏松症中的作用,并探讨骨髓间充质干细胞成骨分化的机制。采用 RT-qPCR、ELISA 和 Western blot 检测 miR-193a、SIRT7 和成骨标志物蛋白的表达水平。通过双荧光素酶报告实验验证 miR-193a 与 SIRT7 之间的相互作用。此外,通过 MTT 检测法检测细胞活力。通过茜素红 s 染色检测骨形成和钙沉积。成功建立去卵巢大鼠模型,通过 HE 染色检测股骨小梁组织。结果表明,骨质疏松症中 miR-193a 表达上调,SIRT7 表达下调。RES 抑制 miR-193a 促进成骨分化。机制上,miR-193a 靶向并负调控 SIRT7。此外,证实 SIRT7 通过 NF-κB 信号通路促进 BMSCs 成骨分化。进一步研究表明,RES 通过 miR-193a/SIRT7 介导的 NF-κB 信号通路发挥其有益作用,从而减轻体内骨质疏松症。本研究表明,RES 调节的 miR-193a 抑制作用负责成骨分化过程中 SIRT7/NF-κB 信号通路的激活,为骨质疏松症的诊断和治疗提供了新的思路。

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