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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.
摘要：
人骨髓间充质干细胞(hBMSCs)具有成骨分化潜能,是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。这里,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。用成骨分化诱导培养基处理hBMSCs用于成骨。用茜素红S(ARS)和碱性磷酸酶(ALP)染色测定hBMSCs矿化结节形成和ALP活性,分别。ICI182780，雌激素受体α（ERα）的拮抗剂用于抑制ERα表达。结果表明，NGR1增强了hBMSC的增殖和迁移。NGR1增加了ALP活性和矿化结节形成以及促进ALP，RUNX2和OCN在hBMSCs中的表达。NGR1在hBMSCs中增强ERα表达并促进GSK-3β/β-catenin信号转导。ICI182780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促进增殖，hBMSCs通过ERα/GSK-3β/β-catenin信号通路迁移和成骨分化。
