Notoginsenoside R1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via ERα/GSK-3β/β-catenin signalling pathway

IF 1.8 4区医学 Q3 PATHOLOGY International Journal of Experimental Pathology Pub Date : 2023-10-30 DOI:10.1111/iep.12494

Wei Lu, Yuanxin Shi, Minglei Qian

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Abstract

Human bone marrow mesenchymal stem cells (hBMSCs) are attractive therapeutic agents for bone tissue regeneration owing to their osteogenic differentiation potential. Notoginsenoside R1 (NGR1) is a novel phytoestrogen with diverse pharmacological activities. Here, we probed whether NGR1 has an effect on the osteogenic differentiation of hBMSCs. EdU, CCK-8 and Transwell assays were used to measure proliferation and migration of hBMSCs after treatment with different doses of NGR1. hBMSCs were treated with osteogenic differentiation induction medium for osteogenesis. Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were used to measure mineralized nodule formation and ALP activity in hBMSCs, respectively. ICI 182780, an antagonist of oestrogen receptor alpha (ERα) was used to inhibit ERα expression. The results showed that NGR1 enhanced hBMSC proliferation and migration. NGR1 increased ALP activity and mineralized nodule formation as well as promoting ALP, RUNX2 and OCN expression in hBMSCs. NGR1 enhanced ERα expression and promoted GSK-3β/β-catenin signal transduction in hBMSCs. ICI 182780 reversed NGR1-mediated activation of the GSK-3β/β-catenin signalling and promoted an effect on hBMSC behaviour. Thus NGR1 promotes proliferation, migration and osteogenic differentiation of hBMSCs via the ERα/GSK-3β/β-catenin signalling pathway.

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三七皂苷R1通过ERα/GSK-3β/β-catenin信号通路促进人骨髓间充质干细胞的成骨分化。

人骨髓间充质干细胞（hBMSCs）由于其成骨分化潜力而成为骨组织再生的有吸引力的治疗剂。三七皂苷R1（NGR1）是一种具有多种药理活性的新型植物雌激素。在此，我们探讨了NGR1是否对hBMSCs的成骨分化有影响。EdU、CCK-8和Transwell测定用于测量用不同剂量的NGR1处理后hBMSCs的增殖和迁移。hBMSCs用成骨分化诱导培养基进行成骨处理。Alizarin红S（ARS）和碱性磷酸酶（ALP）染色分别用于测量hBMSCs中矿化结节的形成和ALP活性。使用雌激素受体α（ERα）拮抗剂ICI 182780抑制ERα的表达。结果表明，NGR1能促进hBMSC的增殖和迁移。NGR1增加了hBMSCs中ALP活性和矿化结节的形成，并促进了ALP、RUNX2和OCN的表达。NGR1增强人骨髓基质干细胞中ERα的表达并促进GSK-3β/β-catenin信号转导。ICI 182780逆转NGR1介导的GSK-3β/β-连环蛋白信号传导的激活，并促进对hBMSC行为的影响。因此，NGR1通过ERα/GSK-3β/β-catenin信号通路促进hBMSCs的增殖、迁移和成骨分化。

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来源期刊

International Journal of Experimental Pathology 医学-病理学

CiteScore

4.50

自引率

3.30%

发文量

审稿时长

>12 weeks

期刊介绍： Experimental Pathology encompasses the use of multidisciplinary scientific techniques to investigate the pathogenesis and progression of pathologic processes. The International Journal of Experimental Pathology - IJEP - publishes papers which afford new and imaginative insights into the basic mechanisms underlying human disease, including in vitro work, animal models, and clinical research. Aiming to report on work that addresses the common theme of mechanism at a cellular and molecular level, IJEP publishes both original experimental investigations and review articles. Recent themes for review series have covered topics as diverse as "Viruses and Cancer", "Granulomatous Diseases", "Stem cells" and "Cardiovascular Pathology".