色谱 ›› 2017, Vol. 35 ›› Issue (4): 458-465.DOI: 10.3724/SP.J.1123.2016.11004

• 研究论文 • 上一篇    下一篇

微流控芯片流体剪切力和肿瘤坏死因子-α共同作用对大鼠软骨细胞表型的影响

石杨1, 盛坤2, 张敏1, 李洪敬2, 秦建华1   

  1. 1. 中国科学院大连化学物理研究所, 辽宁 大连 116023;
    2. 大连医科大学第一附属医院, 辽宁 大连 116000
  • 收稿日期:2016-11-03 出版日期:2017-04-08 发布日期:2013-07-30
  • 通讯作者: 秦建华,E-mail:jhqin@dicp.ac.cn;李洪敬,E-mail:hongjingl@hotmail.com.
  • 基金资助:

    国家自然科学基金项目(81603075);中国博士后科学基金项目(2016M591463).

Effects of combined the fluid shear stress and tumor necrosis factor-α on cartilage phenotype in a dynamic microfluidic chip

SHI Yang1, SHENG Kun2, ZHANG Min1, LI Hongjing2, QIN Jianhua1   

  1. 1. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;
    2. First Affiliated Hospital of Dalian Medical University, Dalian 116000, China
  • Received:2016-11-03 Online:2017-04-08 Published:2013-07-30
  • Supported by:

    National Natural Science Foundation of China (No. 81603075); China Postdoctoral Science Foundation (No. 2016M591463).

摘要:

流体剪切力是生物体内普遍存在的一种生物力学形式,是细胞微环境的重要组成部分,对细胞多种生物学行为有重要调节作用。该研究以微流控芯片技术为基础,建立了一种基于流阻原理能同时产生4个不同大小流体剪切力的微流控芯片平台,用以研究低流速的流体剪切力对大鼠原代软骨细胞表型维持的影响。结果表明,流体剪切力可促进软骨细胞的表型维持。还加入了肿瘤坏死因子-α(TNF-α),考察流体剪切力和TNF-α共同作用对软骨细胞表型的影响。结果表明,在剪切力和TNF-α共同作用下,软骨细胞的Ⅱ型胶原和蛋白多糖表达明显下调。该研究为软骨组织工程和骨性关节炎的疾病研究提供有力的研究平台,为骨关节疾病治疗和防治提供了理论依据。

关键词: 流体剪切力, 软骨表型, 微流控芯片, 肿瘤坏死因子-α

Abstract:

Fluid shear stress as a common form of biomechanics plays an important role in maintaining cell morphology, cell secretion and function in microenvironment. Herein, we proposed a microfluidic platform which could generate four different intensities of fluid shear to study the cellular effects of fluid shear stress on chondrocyte phenotype under low flow condition. Under low flow condition, the primary chondrocytes could keep good activity and morphology. With the increase of shear force, the expressions of collagen type Ⅱ and aggrecan in primary chondrocyte were up-regulated. At the same time, the expressions of collagen type Ⅰ increased. These results indicated that fluid shear stress could improve chondrocyte phenotype maintaining. Moreover, increase of the shear force also accelerated the dedifferentiation of chondrocytes. Tumor necrosis factor-α (TNF-α) plays a negative role in maintaining chondrocyte phenotype. The interaction effect of fluid shear stress and TNF-α on chondrocyte phenotype was investigated on this platform. The results showed that under the combined effects of the shear force and TNF-α, the expressions of collagen type Ⅱ and aggrecan of chondrocytes were significantly down-regulated. This method provided a powerful platform for cartilage tissue engineering and osteoarthritis disease research, and gave a theoretical basis for the joint disease treatment and prevention.

Key words: (TNF-α), cartilage phenotype, fluid shear stress, microfluidic chip, tumor necrosis factor-&alpha

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