Inhibition of ERK promotes collagen gel compaction and fibrillogenesis to amplify the osteogenesis of human mesenchymal stem cells in three-dimensional collagen I culture.
Inhibition of ERK promotes collagen gel compaction and fibrillogenesis to amplify the osteogenesis of human mesenchymal stem cells in three-dimensional collagen I culture.
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DOI：
10.1089/scd.2008.0075
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发表时间：
2009-03
影响因子：
4
通讯作者：
Plopper GE
中科院分区：
文献类型：
--
作者：
Lund AW;Stegemann JP;Plopper GE
组织形态发生仍然是细胞和发育生物学中理解最少的问题之一。在应用于二维（2D）培养的机制与体内观察到的机制之间存在脱节。三维（3D）培养呈现出一种复杂的刺激，触发细胞反应，这只是部分理解。我们比较了在MEK抑制剂PD98059存在下的人间充质干细胞的2D和3D培养物，以确定ERK在胶原诱导的分化中的作用。3D培养促进人骨髓间充质干细胞向成骨细胞分化。与2D结果相反，添加PD98059在3D培养物中诱导成骨基因表达和基质矿化的显著扩增。ERK的抑制改变了细胞介导的压实，增殖，并导致不同的组织微结构的发展。因此，我们认为在3D中重组胶原的能力是ERK介导的成骨分化的重要步骤。这项工作的目的是提出成骨分化和hMSC定向胶原I重塑之间的相关性。我们提出了一个潜在的机械链接（ERK），通过该三维的工程组织的行为，以差异诱导和维持细胞表型在组织发育过程中。
Tissue morphogenesis remains one of the least understood problems in cell and developmental biology. There is a disconnect between the mechanisms that apply to two dimensional (2D) cultures and those seen in vivo. Three dimensional (3D) culture presents a complex stimulus triggering cellular responses that are only partially understood. We compared 2D and 3D cultures of human mesenchymal stem cells in the presence of the MEK inhibitor, PD98059, to determine the role of ERK in collagen induced differentiation. 3D collagen I culture enhanced and accelerated the osteogenic differentiation of human mesenchymal stem cells. Contrary to 2D results, the addition of PD98059 induced a significant amplification of osteogenic gene expression and matrix mineralization in 3D cultures. The inhibition of ERK altered cell-mediated compaction, proliferation and resulted in the development of distinct tissue microstructure. Therefore, we suggest that the ability to reorganize collagen in 3D is an important step in ERK mediated osteogenic differentiation. This work aims to propose a correlation between osteogenic differentiation and hMSC directed collagen I remodeling. We present a potential mechanistic link (ERK) through which the three dimensionality of an engineered tissue acts to differentially induce and maintain cellular phenotype during tissue development.
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影响因子：
4
作者：
Liao, Qing-Chuan;Li, Ya-Lin;Qin, Yan-Fang;Quarles, L. Darryl;Xu, Kang-Kang;Li, Rong;Zhou, Hong-Hao;Xiao, Zhou-Sheng
通讯作者：
Xiao, Zhou-Sheng
影响因子：
9.8
作者：
Constant, Vanessa A.;Gagnon, AnneMarie;Sorisky, Alexander
通讯作者：
Sorisky, Alexander
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
3.3
作者：
Huang, S;Chen, CS;Ingber, DE
通讯作者：
Ingber, DE
DOI：
10.1016/j.bbrc.2007.02.057
发表时间：
2007-04-20
影响因子：
3.1
作者：
Chen, Tain-Hsiung;Chen, Wei-Ming;Hung, Shih-Chieh
通讯作者：
Hung, Shih-Chieh