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姜黄素通过激活 TGF-β1/Smad3 信号通路促进肌腱干细胞介导的肌腱修复。

Galangin Promotes Tendon Repair Mediated by Tendon-Derived Stem Cells through Activating the TGF-β1/Smad3 Signaling Pathway.

机构信息

Department of Foot and Ankle Surgery, Nanchang Hongdu Hospital of Traditional Chinese Medicine.

出版信息

Chem Pharm Bull (Tokyo). 2024;72(7):669-675. doi: 10.1248/cpb.c24-00117.

DOI:10.1248/cpb.c24-00117
PMID:39010213
Abstract

Tendon injury is a prevalent orthopedic disease that currently lacks effective treatment. Galangin (GLN) is a vital flavonoid found abundantly in galangal and is known for its natural activity. This study aimed to investigate the GLN-mediated molecular mechanism of tendon-derived stem cells (TDSCs) in tendon repair. The TDSCs were characterized using alkaline phosphatase staining, alizarin red S staining, oil red O staining, and flow cytometry. The effect of GLN treatment on collagen deposition was evaluated using Sirius red staining and quantitative (q)PCR, while a Western bot was used to assess protein levels and analyze pathways. Results showed that GLN treatment not only increased the collagen deposition but also elevated the mRNA expression and protein levels of multiple tendon markers like collagen type I alpha 1 (COL1A1), decorin (DCN) and tenomodulin (TNMD) in TDSCs. Moreover, GLN was also found to upregulate the protein levels of transforming growth factor β1 (TGF-β1) and p-Smad3 to activate the TGF-β1/Smad3 signaling pathway, while GLN mediated collagen deposition in TDSCs was reversed by LY3200882, a TGF-β receptor inhibitor. The study concluded that GLN-mediated TDSCs enhanced tendon repair by activating the TGF-β1/Smad3 signaling pathway, suggesting a novel therapeutic option in treating tendon repair.

摘要

肌腱损伤是一种常见的骨科疾病,目前缺乏有效的治疗方法。高良姜素(GLN)是一种重要的类黄酮,在高良姜中含量丰富,具有天然活性。本研究旨在探讨 GLN 介导的肌腱源性干细胞(TDSCs)在肌腱修复中的分子机制。采用碱性磷酸酶染色、茜素红 S 染色、油红 O 染色和流式细胞术对 TDSCs 进行鉴定。采用天狼猩红染色和定量(q)PCR 评估 GLN 处理对胶原蛋白沉积的影响,采用 Western blot 分析蛋白水平和通路。结果表明,GLN 处理不仅增加了胶原蛋白的沉积,还提高了 TDSCs 中多种肌腱标志物如胶原 I 型 α1(COL1A1)、核心蛋白聚糖(DCN)和腱调蛋白(TNMD)的 mRNA 表达和蛋白水平。此外,还发现 GLN 上调了转化生长因子 β1(TGF-β1)和 p-Smad3 的蛋白水平,激活 TGF-β1/Smad3 信号通路,而 TGF-β 受体抑制剂 LY3200882 逆转了 GLN 介导的 TDSCs 胶原蛋白沉积。研究结论为 GLN 介导的 TDSCs 通过激活 TGF-β1/Smad3 信号通路增强肌腱修复提供了新的治疗选择。

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