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

doi:10.3969/j.issn.1006-5725.2026.02.014

实用医学杂志 ›› 2026, Vol. 42 ›› Issue (2): 285-294.doi: 10.3969/j.issn.1006-5725.2026.02.014

• 专题报道：骨科 • 上一篇

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^1,²,陈嘉怡¹,郑臣校¹,郑雨中¹,黄枫³()

^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 接受日期:2025-11-28 出版日期:2026-01-25 发布日期:2026-01-22
通讯作者: 黄枫 E-mail:huangfeng@gzucm.edu.cn
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^1,²,Jiayi CHEN¹,Chenxiao ZHENG¹,Yuzhong ZHENG¹,Feng HUANG³()

^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:2025-10-25 Revised:2025-11-28 Accepted:2025-11-28 Online:2026-01-25 Published:2026-01-22
Contact: Feng HUANG E-mail:huangfeng@gzucm.edu.cn

摘要/Abstract

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。

关键词: 伤科九味健骨片, 牵张成骨, 间充质干细胞, 细胞迁移, 成骨分化, Sdf-1/Cxcr4轴

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.

Key words: Shangke Jiuwei Jiangu tablet, distraction osteogenesis, mesenchymal stem cell, cell migration, osteogenic differentiation, Sdf-1/Cxcr4 axis

中图分类号:

R269

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.

Feifan LUAN,Jiayi CHEN,Chenxiao ZHENG,Yuzhong ZHENG,Feng HUANG. 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[J]. The Journal of Practical Medicine, 2026, 42(2): 285-294.

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参考文献 30

[1]	BORZUNOV D Y， KOLCHIN S N， MALKOVA T A. Role of the Ilizarov non-free bone plasty in the management of long bone defects and nonunion： Problems solved and unsolved［J］. World J Orthop， 2020，11（6）：304-318. doi： 10.5312/wjo.v11.i6.304 . doi: 10.5312/wjo.v11.i6.304
[2]	MENDOZA ISAULA D A， YANOSHAK E， SQUEO G， et al. Nonoral feeding does not predict the occurrence of bone healing complications in mandibular distraction osteogenesis［J］. J Craniofac Surg， 2025， 36（8）：2811-2814. doi： 10.1097/SCS. 0000000000011778 . doi: 10.1097/SCS. 0000000000011778
[3]	LIU Z， LIU Q， GUO H， et al. Overview of physical and pharmacological therapy in enhancing bone regeneration formation during distraction osteogenesis［J］. Front Cell Dev Biol， 2022，10： 837430. doi： 10.3389/fcell.2022.837430 . doi: 10.3389/fcell.2022.837430
[4]	WANG Z， REN L， LI Z， et al. Impact of different cell types on the osteogenic differentiation process of mesenchymal stem cells［J］. Stem Cells Int， 2025，2025：5551222. doi： 10.1155/sci/5551222 . doi: 10.1155/sci/5551222
[5]	LI X L， ZHAO Y Q， MIAO L， et al. Strategies for promoting neurovascularization in bone regeneration［J］. Mil Med Res， 2025，12（1）：9. doi： 10.1186/s40779-025-00596-1 . doi: 10.1186/s40779-025-00596-1
[6]	CHENG G， WANG X， ZHANG F， et al. Reparative homing of bone mesenchymal stem cells induced by iMSCs via the SDF-1/CXCR4 axis for articular cartilage defect restoration［J］. Biomed Pharmacother， 2024，181：117649. doi： 10.1016/j.biopha. 2024. 117649 . doi: 10.1016/j.biopha. 2024. 117649
[7]	ZHANG H， LI X， LI J， et al. SDF-1 mediates mesenchymal stem cell recruitment and migration via the SDF-1/CXCR4 axis in bone defect［J］. J Bone Miner Metab， 2021， 39（2）： 126-138. doi： 10.1007/s00774-020-01122-0 . doi: 10.1007/s00774-020-01122-0
[8]	邓志，谢义松，邹传运. 活血壮骨方联合经皮椎体成形术治疗骨质疏松性椎体压缩骨折的疗效及对患者骨代谢指标、骨密度的影响［J］. 实用医学杂志， 2025， 41（10）： 1584-1589. doi： 10.3969/j.issn.1006-5725.2025.10.022 . doi: 10.3969/j.issn.1006-5725.2025.10.022
[9]	李儒杰，寇楠，庞超平，等. 补肾助阳健骨方对脾肾气阳两虚证老年骨质疏松性脊柱压缩性骨折患者的临床疗效［J］. 中成药， 2024， 46（1）： 337-339. doi： 10.3969/j.issn.1001-1528. 2024. 01.059 . doi: 10.3969/j.issn.1001-1528. 2024. 01.059
[10]	刘庆阳，史毅，王惠东，等. 兔骨髓间充质干细胞的分离、培养与鉴定［J］. 组织工程与重建外科杂志， 2008， 4（2）： 69-72. doi： 10.3969/j.issn.1673-0364.a308 . doi: 10.3969/j.issn.1673-0364.a308
[11]	KING J S， WAN M， KIM A， et al. Effects of aging on the immune and periosteal response to fracture injury［J］. Bone， 2025，198：117524. doi： 10.1101/2024.11.06.622348 . doi: 10.1101/2024.11.06.622348
[12]	BURGAN J， RAHMATI M， LEE M， et al. Innate immune response to bone fracture healing［J］. Bone， 2025，190：117327. doi： 10.1016/j.bone.2024.117327 . doi: 10.1016/j.bone.2024.117327
[13]	SHI L， CHEN L， GAO X， et al. Comparison of different sources of mesenchymal stem cells： Focus on inflammatory bowel disease［J］. Inflammopharmacology， 2024， 32（3）： 1721-1742. doi： 10.1007/s10787-024-01468-1 . doi: 10.1007/s10787-024-01468-1
[14]	LI Z， LIU J， LI C， et al. Advances in the application of bone transport techniques in the treatment of bone nonunion and bone defects［J］. Orthop Surg， 2023，15（12）：3046-3054. doi： 10.1111/os.13936 . doi: 10.1111/os.13936
[15]	ZHENG K， YU X C， CAI J， et al. Management of bone defects and complications after bone tumor resection using ilizarov method［J］. Orthop Surg， 2025，17（2）：492-499. doi： 10.1111/os.14318 . doi: 10.1111/os.14318
[16]	JENNES M E， HEY J， BARTZELA T N， et al. Esthetic and functional rehabilitation of severe facial asymmetry and dental attrition in a patient with hemifacial microsomia： An interdisciplinary treatment outcome［J］. Quintessence Int， 2022，53（6）：534-545. doi： 10.3290/j.qi.b2793257 . doi: 10.3290/j.qi.b2793257
[17]	DOMINGUES M F， CARVALHO M S， SANJUAN-ALBERTE P， et al. Synthetic scaffolds functionalized with mesenchymal stem/stromal cells-derived extracellular matrix for bone tissue engineering： a review［J］. RSC Adv， 2025， 15（38）： 31812-31829. doi： 10.1039/d5ra02106e . doi: 10.1039/d5ra02106e
[18]	WANG X， YU Y， ZHANG R， et al. Enhanced bone regeneration by schwann cells through coupling of osteogenesis and angiogenesis via β-catenin signaling in a preclinical model of distraction osteogenesis［J］. Int J Med Sci， 2025，22（1）：209-226. doi： 10.7150/ijms.100854 . doi: 10.7150/ijms.100854
[19]	ARYA PN， SARANYA I， SELVAMURUGAN N. Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiation［J］. World J Stem Cells， 2024， 16（2）：102-113. doi： 10.4252/wjsc.v16.i2.102 . doi: 10.4252/wjsc.v16.i2.102
[20]	LI S， XING F， LUO R， et al. Clinical effectiveness of platelet-rich plasma for long-bone delayed union and nonunion： A systematic review and meta-analysis［J］. Front Med （Lausanne）， 2021，8：771252. doi： 10.3389/fmed.2021.771252 . doi: 10.3389/fmed.2021.771252
[21]	王璠琛，何琪，肖嘉聪，等. “肾主骨”理论“髓变先于骨变”的肾-髓-骨调节机制构建［J］. 中国骨质疏松杂志，2023，29（9）：1354-1361. doi： 10.3969/j.issn.1006-7108.2023.09.018 . doi: 10.3969/j.issn.1006-7108.2023.09.018
[22]	FU R， FENG Y， BERTRAND D， et al. Enhancing the efficiency of distraction osteogenesis through rate-varying distraction： A computational study［J］. Int J Mol Sci， 2021，22（21）：11734. doi： 10.3390/ijms222111734 . doi: 10.3390/ijms222111734
[23]	许旻鸣，楼红侃，高麟超，等. 补肾活血方促进骨髓间充质干细胞的成骨及其防治大鼠骨质疏松症机制研究［J］. 中华中医药学刊， 2024， 42（9）： 144-150. doi： 10.13193/j.issn.1673-7717.2024.09.029 . doi: 10.13193/j.issn.1673-7717.2024.09.029
[24]	秧荣昆，关智宇. 基于肾主骨理论探讨杜仲通过调控OPG/RANKL/RANK通路对去势骨质疏松大鼠的影响［J］. 中成药， 2023， 45（1）：70-74. doi：10.3969/j.issn.1001-1528. 2023. 01.013 . doi: 10.3969/j.issn.1001-1528. 2023. 01.013
[25]	付夜平，杨芳，孙鑫，等. “脾肾相关”治法SDF-1/CXCR4通路对BMSCs成肌、MDSCs成骨分化的影响［J］. 中国骨质疏松杂志，2024，30（9）：1255-1260，1274. doi： 10.3969/j.issn.1006-7108.2024.09.002 . doi: 10.3969/j.issn.1006-7108.2024.09.002
[26]	ZHAO A， CHUNG M， YANG Y， et al. The SDF-1/CXCR4 signaling pathway directs the migration of systemically transplanted bone marrow mesenchymal stem cells towards the lesion site in a rat model of spinal cord injury［J］. Curr Stem Cell Res Ther， 2023， 18（2）： 216-230. doi： 10.2174/1574888X17666220510163245 . doi: 10.2174/1574888X17666220510163245
[27]	王瑞芳，杨迎春，乔海兵，等. 龙胆苦苷调节SDF-1/CXCR4信号通路对人骨髓间充质干细胞成骨分化的影响［J］. 细胞与分子免疫学杂志， 2025， 41（9）： 784-789. doi：10.13423/j.cnki.cjcmi.009980 . doi: 10.13423/j.cnki.cjcmi.009980
[28]	陈玄，陈娟，谢丽华，等. 骨碎补-续断药对对成骨/破骨代谢的双向调控作用及其对Hif1ɑ基因的影响［J］. 中国骨质疏松杂志， 2023， 29（1）： 64-69. doi： 10.3969/j.issn.1006-7108. 2023.01.012 . doi: 10.3969/j.issn.1006-7108. 2023.01.012
[29]	XUE Y， LI Z， WANG Y， et al. Role of the HIF‑1α/SDF‑1/CXCR4 signaling axis in accelerated fracture healing after craniocerebral injury［J］. Mol Med Rep， 2020， 22（4）： 2767-2774. doi： 10.3892/mmr.2020.11361 . doi: 10.3892/mmr.2020.11361
[30]	刘胜，刘玲，房纬，等. 独活续断汤口服和离子导入治疗肝肾亏虚型膝骨关节炎患者疗效及对膝关节液SDF-1/CXCR4信号通路的影响［J］. 中国实验方剂学杂志， 2020， 26（5）： 69-74. doi： 10.13422/j.cnki.syfjx.20192122 . doi: 10.13422/j.cnki.syfjx.20192122

引物	序列（5'—3'）	PCR产物大小/bp
Runx2（Rabbit）-RT-F	GACCACCCAGCCGAACT	154
Runx2（Rabbit）-RT-R	CCGCCATGACAGTAACCA	154
Cxcr4（Rabbit）-RT-F	CTTCCTGCCCACCATC	185
Cxcr4（Rabbit）-RT-R	TCGCCACAGCATCCAC	185
Sdf?1（Rabbit）-RT-F	CTCAGTGAAGAGGCTAAT	193
Sdf?1（Rabbit）-RT-R	TTGGGTTGTGGAATAA	193
Ocn（Rabbit）-RT-F	ACCGCCAGACTCAGCA	107
Ocn（Rabbit）-RT-R	TCAGGTGGGTGTCAAGG	107
Gapdh（Rabbit）-RT-F	GTGATGGGCGTGAACC	122
Gapdh（Rabbit）-RT-R	TCCACAATGCCGAAGT	122

组别	Cxcr 4	Sdf?1	Runx2	Ocn
空白对照组	1.00 ± 0.05^?	1.00 ± 0.03^?	1.00 ± 0.04^?	1.00 ± 0.04^?
含药血清组	2.65 ± 0.09	2.61 ± 0.20	1.49 ± 0.04	1.89 ± 0.07
空白血清组	1.01 ± 0.05^?	1.07 ± 0.08^?	1.00 ± 0.02^?	1.02 ± 0.07^?
F值	582.832	152.354	176.762	195.443
P值	< 0.000 1	< 0.000 1	< 0.000 1	< 0.000 1

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

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

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