专题报道:骨科

伤科九味健骨片通过调控基质细胞衍生因子-1α/C-X-C趋化因子受体4型轴对骨髓间充质干细胞成骨分化及牵张成骨的影响

  • 栾非凡 ,
  • 陈嘉怡 ,
  • 郑臣校 ,
  • 郑雨中 ,
  • 黄枫
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  • 1.广州中医药大学附属中山中医院创伤骨科 广东 中山 528400
    2.广州中医药大学第一临床医学院
    3.广州中医药大学第一附属医院创伤骨科 广东 广州 510405

收稿日期: 2025-10-25

  修回日期: 2025-11-28

  录用日期: 2025-11-28

  网络出版日期: 2026-01-22

基金资助

广东省基础与应用基础研究基金项目(2022B1515230008);中山市社会公益与基础研究专项资金项目(2024B1113);广州中医药大学校院联合科技创新基金项目(GZYZS2024G21);中山市医学科研项目(20241A020220)

Effect of Shangke Jiuwei Jiangu Tablet on osteogenic differentiation and distraction osteogenesis of bone marrow mesenchymal stem cells by regulating stromal cell-derived factor-1 α/C-X-C chemokine receptor type 4 axis

  • Feifan LUAN ,
  • Jiayi CHEN ,
  • Chenxiao ZHENG ,
  • Yuzhong ZHENG ,
  • Feng HUANG
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  • 1.Trauma Orthopedics,Zhongshan Hospital Affiliated to Guangzhou University of Chinese Medicine,Zhongshan 528400,Guangdong,China
    2.First Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510499,Guangdong,China
    3.Trauma Orthopedics,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China

Received date: 2025-10-25

  Revised date: 2025-11-28

  Accepted date: 2025-11-28

  Online published: 2026-01-22

摘要

目的 探讨补肾活血中药复方伤科九味健骨片对牵张成骨模型骨愈合的影响,并从分子及细胞水平初步阐明其作用机制。 方法 建立家兔胫骨牵张成骨模型,随机分为对照组、低、中、高剂量中药组。干预结束后,通过Micro-CT扫描及三维重建评估骨痂形态,计算骨体积分数(BV/TV)和骨矿物密度(BMD);组织切片行HE染色观察骨痂组织学结构;体外实验采用Transwell检测含药血清对骨髓间充质干细胞(MSCs)迁移能力的影响;通过成骨/成脂诱导分化实验评估细胞定向分化倾向;RT-PCR法检测MSCs中Sdf-1、Cxcr4、Runx2及Ocn mRNA表达水平。 结果 与对照组相比,中药各组Micro-CT显示骨折线宽度减小、骨痂量增多,高剂量组效果最显著,骨痂连续、骨折线基本消失;BV/TV和BMD测定显示中药组骨愈合指标显著提高(P < 0.05),且呈剂量依赖性。组织学显示高剂量组骨痂成熟度最高,编织骨-板层骨转化活跃。体外实验中,含药血清组MSCs迁移率显著升高(P < 0.000 1),成骨分化增强而成脂分化被抑制,Sdf-1、Cxcr4、Runx2及Ocn mRNA表达均显著上调(P < 0.000 1)。 结论 伤科九味健骨片可能通过激活Sdf-1/Cxcr4信号轴促进MSCs迁移,诱导成骨分化,同时抑制成脂分化,从而在体内外协同促进牵张成骨过程中的新骨形成、矿化及成熟,其作用机制与中医“补肾活血健骨”治法高度吻合。

本文引用格式

栾非凡 , 陈嘉怡 , 郑臣校 , 郑雨中 , 黄枫 . 伤科九味健骨片通过调控基质细胞衍生因子-1α/C-X-C趋化因子受体4型轴对骨髓间充质干细胞成骨分化及牵张成骨的影响[J]. 实用医学杂志, 2026 , 42(2) : 285 -294 . DOI: 10.3969/j.issn.1006-5725.2026.02.014

Abstract

Objective To explore the effects of the Bushen Huoxue traditional Chinese medicine, the compound Shangke Jiuwei Jiangu tablet, on bone healing in the distraction osteogenesis model, and to preliminarily expound its action mechanism at the molecular and cellular levels. Methods The tibial distraction osteogenesis models of rabbits were constructed and then randomly divided into a control group, a low-dose traditional Chinese medicine (TCM) group, a medium-dose TCM group, and a high-dose TCM group. After the intervention, the morphology of the bone callus was evaluated through Micro-CT scanning and three-dimensional reconstruction, and the bone volume fraction (BV/TV) and bone mineral density (BMD) were calculated. HE staining was carried out on tissue sections to observe the histological structure of the callus. In the in-vitro experiment, the effects of drug serum on the migration ability of bone marrow mesenchymal stem cells (MSCs) were detected using the Transwell assay. The tendency of cell directional differentiation was evaluated through osteogenic/adipogenic induction differentiation experiments. The expression levels of Sdf-1, Cxcr4, Runx2, and Ocn mRNA in MSCs were detected by RT-PCR. Results Compared with the control group, Micro-CT revealed that the width of the fracture line decreased and the number of calluses increased in all TCM groups. The effect was most significant in the high-dose group, where continuous calluses were observed and the fracture line basically disappeared. BV/TV and BMD detection indicated that the bone healing indexes were significantly improved in the TCM groups (P < 0.05), showing a dose-dependent relationship. Histological examination showed that the callus maturity was the highest in the high-dose group, and the transformation from braided bone to lamellar bone was active. In the in-vitro experiment, the migration rate of MSCs was significantly increased in the drug serum group (P < 0.000 1). Osteogenic differentiation was enhanced while adipogenic differentiation was inhibited, and the expressions of Sdf-1, Cxcr4, Runx2, and Ocn mRNA were all significantly up-regulated (P < 0.000 1). Conclusions Shangke Jiuwei Jiangu tablets may promote the migration of MSCs by activating the Sdf-1/Cxcr4 signaling axis and induce their osteogenic differentiation. Consequently, this can promote the formation, mineralization, and maturation of new bones during the distraction osteogenesis process both in vivo and in vitro. Its mechanism of action highly aligns with the Bushen Huoxue Jiangu method in TCM.

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