Glycyrrhizic Acid Promotes Osteogenic Differentiation of Human Bone Marrow Stromal Cells by Activating the Wnt/β-Catenin Signaling Pathway.

Glycyrrhizic Acid Promotes Osteogenic Differentiation of Human Bone Marrow Stromal Cells by Activating the Wnt/β-Catenin Signaling Pathway.
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甘草酸通过激活 Wnt/β-Catenin 信号通路促进人骨髓基质细胞成骨分化

DOI:
10.3389/fphar.2021.607635
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发表时间:
2021
影响因子:
5.6
通讯作者:
Xue D
Xue D
中科院分区:
医学2区
文献类型:
--
作者:
Bai J;Xu J;Hang K;Kuang Z;Ying L;Zhou C;Ni L;Wang Y;Xue D

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甘草酸(GA)是从甘草中分离出的一种主要的三萜苷,具有抑制破骨细胞生成的作用。然而,还没有关于GA对成骨分化的影响的报道。因此,本研究旨在探讨GA对成骨的影响及其作用机制。CCK-8阵列用于评估细胞活力。通过实时定量PCR、免疫印迹和免疫荧光分析检测其成骨能力。ALP染色和ARS分别用于评估ALP活性和矿化。设计GA-GelMA水凝胶以通过放射学分析和组织学评价来验证GA在体内的治疗效果。我们的研究结果表明,GA对人骨髓基质细胞(hBMSCs)的活力和增殖没有显着影响。GA促进成骨分化,增加钙沉积。GA处理后,活性β-catenin蛋白与总β-catenin蛋白的比例增加。Wnt/catenin信号传导抑制剂部分减弱GA对成骨分化的影响。在小鼠股骨骨折模型中,GA-GelMA水凝胶加速了骨愈合。结果表明GA通过调节Wnt/β-catenin信号通路促进hBMSCs向成骨细胞分化。GA-GelMA水凝胶促进骨折愈合。GA具有作为骨缺损的成本效益治疗的潜力。
Glycyrrhizic acid (GA) is a major triterpene glycoside isolated from liquorice root that has been shown to inhibit osteoclastogenesis. However, there have been no reports regarding the effect of GA on osteogenic differentiation. Therefore, this study was performed to explore the effects and mechanism of action of GA on osteogenesis. A CCK-8 array was used to assess cell viability. The osteogenic capability was investigated by real-time quantitative PCR, western blotting and immunofluorescence analyses. ALP staining and ARS were used to evaluate ALP activity and mineralization, respectively. GA-GelMA hydrogels were designed to verify the therapeutic effects of GA in vivo by radiographic analysis and histological evaluation. Our results show that GA had no significant influence on the viability or proliferation of human bone marrow stromal cells (hBMSCs). GA promoted osteogenic differentiation and enhanced calcium deposition. Furthermore, ratio of active β-catenin and total β-catenin protein increased after treatment with GA. Wnt/catenin signaling inhibitor partially attenuated the effects of GA on osteogenic differentiation. In a mouse femoral fracture model, GA-GelMA hydrogels accelerated bone healing. Our results show that GA promotes the osteogenic differentiation of hBMSCs by modulating the Wnt/β-catenin signaling pathway. GA-GelMA hydrogels promoted bone fracture healing. GA has potential as a cost-effective treatment of bone defects.
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