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甘草酸通过激活Wnt/β-连环蛋白信号通路促进人骨髓间充质干细胞的成骨分化。

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

作者信息

Bai Jinwu, Xu Jianxiang, Hang Kai, Kuang Zhihui, Ying Li, Zhou Chenwei, Ni Licheng, Wang Yibo, Xue Deting

机构信息

Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Orthopedics Research Institute, Zhejiang University, Hangzhou, China.

出版信息

Front Pharmacol. 2021 Apr 16;12:607635. doi: 10.3389/fphar.2021.607635. eCollection 2021.

DOI:10.3389/fphar.2021.607635
PMID:33935702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8085383/
Abstract

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 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 -catenin and total -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.

摘要

甘草酸（GA）是从甘草根中分离出的一种主要的三萜糖苷，已被证明可抑制破骨细胞生成。然而，关于GA对成骨分化的影响尚无报道。因此，本研究旨在探讨GA对成骨作用的影响及作用机制。使用CCK-8阵列评估细胞活力。通过实时定量PCR、蛋白质印迹和免疫荧光分析研究成骨能力。分别使用碱性磷酸酶（ALP）染色和茜素红染色（ARS）评估ALP活性和矿化情况。设计GA-甲基丙烯酰化明胶（GelMA）水凝胶，通过影像学分析和组织学评估来验证GA 的治疗效果。我们的结果表明，GA对人骨髓间充质干细胞（hBMSCs）的活力或增殖没有显著影响。GA促进成骨分化并增强钙沉积。此外，用GA处理后，活性β-连环蛋白与总β-连环蛋白的蛋白比例增加。Wnt/β-连环蛋白信号抑制剂部分减弱了GA对成骨分化的影响。在小鼠股骨骨折模型中，GA-GelMA水凝胶加速了骨折愈合。我们的结果表明，GA通过调节Wnt/β-连环蛋白信号通路促进hBMSCs的成骨分化。GA-GelMA水凝胶促进了骨折愈合。GA具有作为骨缺损经济有效治疗方法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/bb593416d6e1/fphar-12-607635-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/c3ac394e238e/fphar-12-607635-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/8722bef02db6/fphar-12-607635-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/eded225e89f0/fphar-12-607635-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/155519c169f3/fphar-12-607635-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/f00a6bea6916/fphar-12-607635-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/8950874472b2/fphar-12-607635-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/bb593416d6e1/fphar-12-607635-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/c3ac394e238e/fphar-12-607635-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/2426f81efdd5/fphar-12-607635-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/8722bef02db6/fphar-12-607635-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/eded225e89f0/fphar-12-607635-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/155519c169f3/fphar-12-607635-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/f00a6bea6916/fphar-12-607635-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/8950874472b2/fphar-12-607635-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/8085383/bb593416d6e1/fphar-12-607635-g008.jpg

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