Metabolic responses induced by compression of chondrocytes in variable-stiffness microenvironments.
Metabolic responses induced by compression of chondrocytes in variable-stiffness microenvironments.
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DOI：
10.1016/j.jbiomech.2017.08.032
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发表时间：
2017-11-07
影响因子：
2.4
通讯作者：
June RK
中科院分区：
文献类型：
--
作者：
McCutchen CN;Zignego DL;June RK
细胞在一个称为机械转导的过程中感知并响应机械负荷。在关节疾病期间，这些过程在软骨的软骨细胞中被破坏。细胞机械转导的一个关键驱动因素是周围基质的刚度。许多细胞被允许组织机械功能的细胞外基质包围。虽然先前的研究表明，细胞外刚度是重要的细胞分化，形态和表型，它仍然在很大程度上是未知的细胞的生物反应，循环负荷如何变化与周围基板刚度的变化。理解这些过程对于理解在日常体内活动期间循环加载的细胞（例如软骨细胞和行走）是重要的。本研究使用高效液相色谱-质谱法来鉴定在低刚度和高刚度环境中循环压缩0 - 30分钟的原代软骨细胞中的代谢组学变化。代谢组学分析揭示了对底物刚度、周期性压缩持续时间以及两者的组合敏感的代谢物和途径，这表明体内细胞外刚度的变化改变了机械敏感性信号传导。我们的研究结果进一步表明，周期性负荷最大限度地减少基质的恶化，并增加软骨细胞中的基质生产。这项研究表明，在体内刚度与体外模型建模，以了解细胞力学转导的重要性。
Cells sense and respond to mechanical loads in a process called mechanotransduction. These processes are disrupted in the chondrocytes of cartilage during joint disease. A key driver of cellular mechanotransduction is the stiffness of the surrounding matrix. Many cells are surrounded by extracellular matrix that allows for tissue mechanical function. Although prior studies demonstrate that extracellular stiffness is important in cell differentiation, morphology and phenotype, it remains largely unknown how a cell’s biological response to cyclical loading varies with changes in surrounding substrate stiffness. Understanding these processes is important for understanding cells that are cyclically loaded during daily in vivo activities (e.g. chondrocytes and walking). This study uses high-performance liquid chromatography - mass spectrometry to identify metabolomic changes in primary chondrocytes under cyclical compression for 0–30 minutes in low- and high- stiffness environments. Metabolomic analysis reveals metabolites and pathways that are sensitive to substrate stiffness, duration of cyclical compression, and a combination of both suggesting changes in extracellular stiffness in vivo alter mechanosensitive signaling. Our results further suggest that cyclical loading minimizes matrix deterioration and increases matrix production in chondrocytes. This study shows the importance of modeling in vivo stiffness with in vitro models to understand cellular mechanotransduction.
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影响因子：
2.4
作者：
Alexopoulos, LG;Williams, GM;Guilak, F
通讯作者：
Guilak, F
DOI：
10.1115/1.429656
发表时间：
2000-06-01
影响因子：
1.7
作者：
Mauck, RL;Soltz, MA;Ateshian, GA
通讯作者：
Ateshian, GA
影响因子：
2.8
作者：
Davisson, T;Kunig, S;Ratcliffe, A
通讯作者：
Ratcliffe, A
影响因子：
4.1
作者：
Bian, Liming;Fong, Jason V.;Hung, Clark T.
通讯作者：
Hung, Clark T.
影响因子：
4.5
作者：
Yu, Haomiao;Li, Yadong;Guo, Ai
通讯作者：
Guo, Ai