Substrate Stiffness Together with Soluble Factors Affects Chondrocyte Mechanoresponses
Substrate Stiffness Together with Soluble Factors Affects Chondrocyte Mechanoresponses
复制标题
基质硬度与可溶性因子一起影响软骨细胞机械反应
DOI：
10.1021/am504135b
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发表时间：
2014-09-24
影响因子：
9.5
通讯作者：
Yang, Liu
中科院分区：
文献类型：
--
作者：
Chen, Cheng;Xie, Jing;Yang, Liu
组织细胞感知并响应基质硬度的差异。在软骨细胞中，已经表明基底硬度调节细胞铺展、增殖、软骨形成基因表达和TGF-β信号传导。但基质硬度和可溶性因子对软骨细胞力学性能的影响尚不清楚。在这项研究中，我们培养山羊关节软骨细胞的聚丙烯酰胺凝胶的1，11，和90千帕（杨氏模量），并测量细胞的刚度，牵引力，并在TGF-β 1或IL-1 β的存在下拉伸的反应。我们发现，TGF-β 1增加细胞刚度和牵引力，增强对拉伸的反应，而IL-1 β增加细胞刚度，但降低牵引力，减弱对拉伸的反应。重要的是，TGF-β 1对软骨细胞力学的影响在90 kPa基质上培养的细胞中是有效的，而IL-1 β对1 kPa基质的影响是有效的。我们还证明，软骨细胞机械反应的这种变化不仅是由于肌动蛋白细胞骨架和粘着斑的变化，而且还由于软骨细胞外基质合成的改变。总之，这些结果提供了深入了解软骨细胞如何整合物理和生化线索来调节其生物力学行为，从而对工程软骨优化机械和生化微环境的设计具有影响。
Tissue cells sense and respond to differences in substrate stiffness. In chondrocytes, it has been shown that substrate stiffness regulates cell spreading, proliferation, chondrogenic gene expression, and TGF-beta signaling. But how the substrate stiffness together with soluble factors influences the mechanical properties of chondrocyte is still unclear. In this study, we cultured goat articular chondrocytes on polyacrylamide gels of 1, 11, and 90 kPa (Young's modulus), and measured cellular stiffness, traction force, and response to stretch in the presence of TGF-beta 1 or IL-1 beta. We found that TGF-beta 1 increased cellular stiffness and traction force and enhanced the response to stretch, while IL-1 beta increased cellular stiffness, but lowered traction force and weakened the response to stretch. Importantly, the effects of TGF-beta 1 on chondrocyte mechanics were potent in cells cultured on 90 kPa substrates, while the effects of IL-1 beta were potent on 1 kPa substrates. We also demonstrated that such changes of chondrocyte mechanoresponse were due to not only the changes of actin cytoskeleton and focal adhesion, but also the alteration of chondrocyte extracellular matrix synthesis. Taken together, these results provide insights into how chondrocytes integrate physical and biochemical cues to regulate their biomechanical behavior, and thus have implications for the design of optimized mechanical and biochemical microenvironments for engineered cartilage.