中国组织工程研究

中国组织工程研究 ›› 2016, Vol. 20 ›› Issue (41): 6098-6104.doi: 10.3969/j.issn.2095-4344.2016.41.003

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

SDF-1/CXCR4信号通路参与骨形态发生蛋白2在诱导骨髓间充质干细胞迁移的作用

杨  毅1，易  蕾2，叶尔扎提•哈加合曼1，特列克•坎扎勒1，金格勒1   

  1. 新疆医科大学第一附属医院，1骨科中心，2神经内科，新疆维吾尔自治区乌鲁木齐市  830054
  • 修回日期:2016-08-22 出版日期:2016-10-07 发布日期:2016-10-07
  • 通讯作者: 金格勒，博士，主任医师，教授，新疆医科大学第一附属医院骨科中心，新疆维吾尔自治区乌鲁木齐市 830054
  • 作者简介:杨毅，男，1981年生，四川省南充市人，汉族， 2010年新疆医科大学毕业，硕士，主治医师，主要从事骨组织工程、脊柱外科、四肢创伤研究。 共同第一作者：易蕾，女，1981年生，四川省成都市人，汉族，2016年新疆医科大学毕业，硕士，医师，主要从事干细胞及神经病学研究。
  • 基金资助:

    国家自然科学基金项目(青年科学基金项目)(81301336)

Stromal cell derived factor-1/chemokine receptor 4 signaling pathway is involved in bone morphogenetic protein 2-induced migration of bone marrow mesenchymal stem cells

Yang Yi1, Yi Lei2, Yeerzhati Hajiaheman1, Telieke Kanzhale1, Jin Ge-le1   

  1. 1Orthopedics Center, 2Department of Neurology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
  • Revised:2016-08-22 Online:2016-10-07 Published:2016-10-07
  • Contact: Jin Ge-le, M.D., Chief physician, Professor, Orthopedics Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
  • About author:Yang Yi, Master, Attending physician, Orthopedics Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China Yi Lei, Master, Physician, Department of Neurology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China Yang Yi and Yi Lei contributed equally to this work.
  • Supported by:

    the National Natural Science Foundation of China, No. 81301336

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被引次数

3

摘要：

文章快速阅读：

文题释义：
归巢效应：是指自体的或外源性骨髓间充质干细胞在多种因素的作用下定向趋向性迁移至损伤组织并定植修复过程。作者所在课题组前期研究发现，重组人骨形态发生蛋白2具有早期诱导种子细胞(骨髓间充质干细胞)动员、迁移至骨缺损部位的能力，并且细胞数量较多；经过外周血管注射标记的骨髓间充质干细胞同样能迁移到复合骨植入部位，但是骨形态发生蛋白2诱导骨髓间充质干细胞归巢至骨形成部位的具体机制仍不明确。
基质细胞衍生因子(stromal cell derived factor，SDF-1)/趋化因子受体(chemokine receptor 4，CXCR4)信号通路：SDF-1属于α类趋化因子，为一种相对分子质量较小的细胞因子。CXCR4是介导SDF-1行使功能的GTP蛋白耦联的跨膜受体，不仅表达于细胞表面，也可在胞浆中检测到。研究发现SDF-1/CXCR4信号通路可能参与骨祖细胞的动员和迁移。

 

摘要
背景：SDF-1/CXCR-4生物轴对多种细胞的趋化能力，使其在多种组织的再生过程中发挥着重要的调控作用，但其是否参与介导骨形态发生蛋白2在骨修复过程中骨髓间充质干细胞归巢目前尚不清楚。
目的：探索SDF-1/CXCR4信号通路在骨形态发生蛋白2诱导小鼠骨髓间充质干细胞迁移中的作用。
方法：取对数生长期骨髓间充质干细胞，分别以0，50，100，200 μg/L SDF-1，0，50，100，200 μg/L骨形态发生蛋白2以及50 μg/L AMD3100进行干预，诱导细胞迁移并Transwell检测。
结果与结论：骨髓间充质干细胞的迁移数量与SDF-1和骨形态发生蛋白2密切相关，并且与SDF-1和骨形态发生蛋白2的浓度成正比，当联合使用SDF-1和骨形态发生蛋白2时，细胞迁移数较单独使用时增多，当质量浓度为200 μg/L时，骨髓间充质干细胞迁移数量最多，并呈“巢穴”样分布。阻断剂AMD3100明显抑制骨形态发生蛋白2诱导骨髓间充质干细胞迁移，但当增加骨形态发生蛋白2浓度达到一定量时，骨髓间充质干细胞迁移数随着骨形态发生蛋白2浓度的增加而增多。提示SDF-1/CXCR4信号通路参与骨形态发生蛋白2诱导骨髓间充质干细胞的迁移。

 

 

关键词: 干细胞, 骨髓干细胞, 信号通路, 骨形态发生蛋白2, 骨髓间充质干细胞, 细胞迁移, 基质细胞衍生因子, 归巢, 骨缺损, 骨再生, 国家自然科学基金

Abstract:

BACKGROUND: Stromal cell derived factor-1 (SDF-1)/chemokine receptor 4 (CXCR-4) biological axis plays a chemotactic role in a variety of cells, making it possible to regulate the regeneration of a variety of tissues. Whether the bidogical is involved in bone morphogenetic protein-2 (BMP-2)-induced homing of bone marrow mesenchymal stem cells, however, is still unclear.
OBJECTIVE: To study the role of SDF-1/CXCR4 signaling pathway in BMP-2-induced migration of mouse bone marrow mesenchymal stem cells.
METHODS: Bone marrow mesenchymal stem cells in logarithmic growth were selected and intervened with SDF-1 (0, 50, 100 and 200 μg/L), BMP-2 (0, 50, 100 and 200 μg/L) and AMD3100 (50 μg/L) to induce cell migration detected by Transwell method.
RESULTS AND CONCLUSION: The migration of bone marrow mesenchymal stem cells was closely related to SDF-1 and BMP-2, and proportional to the concentration of both SDF-1 and BMP-2. When SDF-1 and BMP-2 were used jointly, the number of migrated cells was increased significantly, and highest number of migrated cells was obtained at 200 μg/L. Moreover, these migrated cells showed a nest-like distribution under microscopy. AMD3100 as an inhibitor markedly suppressed the migration of bone marrow mesencnymal stem cells induced by BMP-2, but the number of migrated cells was likely to increase with the increasing concentration of BMP-2 that exceeded a specific value. Overall, our findings show that SDF-1/CXCR4 signaling pathway is an important pathway in BMP-2-induced migration of bone marrow mesenchymal stem cells.

 

 

Key words: Bone Morphogenetic Proteins, Receptors, CXCR4, Tissue Engineering

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