中国组织工程研究

中国组织工程研究 ›› 2016, Vol. 20 ›› Issue (50): 7475-7480.doi: 10.3969/j.issn.2095-4344.2016.50.004

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

小分子药物Kartogenin诱导骨髓间充质干细胞定向分化中基质金属蛋白酶2的表达

王  呈，薄其玉，戴国锋，杨伟巍   

  1. 山东大学齐鲁医院，山东省济南市  250012
  • 修回日期:2016-10-11 出版日期:2016-12-02 发布日期:2016-12-02
  • 通讯作者: 戴国锋，山东大学齐鲁医院，山东省济南市 250012
  • 作者简介:王呈，男，1980年生，山东省烟台市人，汉族，2011年北京大学毕业，博士，主治医师，主要从事骨关节退变及运动损伤研究。
  • 基金资助:

    山东省科技攻关计划项目(2013GSF11826)

Variation of matrix metalloproteinase 2 levels during Kartogenin-induced directional differentiation of human bone marrow mesenchymal stem cells

Wang Cheng, Bo Qi-yu, Dai Guo-feng, Yang Wei-wei   

  1. Qilu Hospital Affiliated to Shandong University, Jinan 250012, Shandong Province, China)
  • Revised:2016-10-11 Online:2016-12-02 Published:2016-12-02
  • Contact: Dai Guo-feng, Qilu Hospital Affiliated to Shandong University, Jinan 250012, Shandong Province, China
  • About author:Wang Cheng, M.D., Attending physician, Qilu Hospital Affiliated to Shandong University, Jinan 250012, Shandong Province, China
  • Supported by:

    the Science and Technology Plan of Shandong Province, No. 2013GSF11826

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被引次数

1

摘要：

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文题释义：
Kartogenin：长期以来科学家们都致力于寻找可再生软骨的方法，这是对抗骨关节炎的核心难题，2012年4月5日，Science在线报道了Kartogenin(KGN)的发现，该小分子是一种smad4/smad5通路激活剂，拥有极强的促软骨分化能力，能有效地促进间充质干细胞向软骨细胞分化。这些研究成果为软骨修复提供了新的线索。
基质金属蛋白酶2：基质金属蛋白酶可降解关节软骨中的胶原蛋白、蛋白多糖和其他细胞外基质大分子，在骨关节炎的发展过程中起重要作用，软骨细胞外基质的主要成分为II型胶原和蛋白聚糖，MMPs家族中基质金属蛋白酶2(MMP-2)作为进一步分解代谢胶原裂解产物的明胶酶，近年来被认为与软骨损伤和退变的病理过程明显相关。

 

摘要
背景：体外实验发现小分子药物Kartogenin(KGN)能诱导间充质干细胞转变成为软骨细胞，KGN的发现为人们找到了修复软骨的新途径，未来很有希望成为新型骨关节炎治疗药物。
目的：通过体外实验观察小分子药物KGN 在骨髓间充质干细胞定向分化为软骨细胞的过程中的诱导作用。
方法：体外传代培养人骨髓间充质干细胞至对数生长期，分为空白对照组、1 μmol/L KGN组和10 μmol/L KGN组，3组KGN的终浓度分别为0，1 和10 μmol/L，培养72 h后通过显微镜检骨髓间充质干细胞的增生和分化情况，用酶联免疫吸附实验检测上清中软骨代谢降解标记物基质金属蛋白酶2水平，用免疫荧光染色技术观察Ⅱ型胶原蛋白表达情况。
结果与结论：镜检发现随着KGN药物浓度的增高能明显促进骨髓间充质干细胞的增生和分化；免疫荧光染色结果显示随着KGN浓度的增高Ⅱ型胶原蛋白的表达增加；而随着KGN药物浓度增加，基质金属蛋白酶2的表达随之降低。提示小分子药物KGN能诱导人骨髓间充质干细胞向软骨细胞定向分化，且随着药物浓度的增加，软骨细胞外基质的破坏也随之被抑制。

 

 

关键词: 干细胞, 骨髓干细胞, 骨关节炎, Kartogenin(KGN), 基质金属蛋白酶2, Ⅱ型胶原, 软骨分化

Abstract:

BACKGROUND: Kartogenin can induce chondrogenic differentiation of mesenchymal stem cells as reported in in vitro experiments. The discovery of Kartogenin finds a novel path to cartilage repair, and it is expected to develop into a new drug to treat osteoarthritis.
OBJECTIVE: To observe the inductive role of Kartogenin in the process of human bone marrow mesenchymal stem cells differentiating into chondrocytes in vitro.
METHODS: In vitro cultured human bone marrow mesenchymal stem cells were grown to the logarithmic phase, and then divided into control group (0 μmol/L Kartogenin), 1 μmol/L Kartogenin group, and 10 μmol/L Kartogenin group. After 72 hours of culture, cell proliferation and differentiation were observed microscopically. Matrix metalloproteinase 2 and type II collagen levels in the cell supernatant were detected by enzyme linked immunosorbent assay and immunofluorescence staining, respectively.
RESULTS AND CONCLUSION: Under the microscope, Kartogenin was shown to significantly promote the proliferation and differentiation of human bone marrow mesenchymal stem cells. With the increase of Kartogenin concentrations, the level of type II collagen was increased, while the level of matrix metalloproteinase 2 was decreased. These findings indicate that Kartogenin can induce human bone marrow mesenchymal stem cells to differentiate into chondrocytes, and with the increase of Kartogenin concentration, destruction of the cartilage extracellular matrix may be inhibited.

 

 

Key words: Stem Cells, Matrix Metalloproteinase 2, Collagen Type II

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