The Role of Collagen Crosslinking in Differentiation of Human Mesenchymal Stem Cells and MC3T3-E1 Cells
The Role of Collagen Crosslinking in Differentiation of Human Mesenchymal Stem Cells and MC3T3-E1 Cells
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DOI：
10.1089/ten.tea.2009.0011
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发表时间：
2009-12-01
影响因子：
4.1
通讯作者：
de Boer, Jan
中科院分区：
文献类型：
--
作者：
Fernandes, Hugo;Dechering, Koen;de Boer, Jan
胶原蛋白是骨细胞外基质的主要蛋白质组分，并且其具有结构和指导性质。胶原蛋白经历许多翻译后修饰，包括广泛的交联。尽管有缺陷的交联与人类综合征有关（例如，骨生成障碍或埃勒斯-当洛斯综合征），但不清楚在骨形成过程中胶原蛋白的指导性质需要交联到什么程度。在这里，我们报告说，在小鼠前成骨细胞系MC 3 T3-E1的胶原交联抑制损害成骨程序。β-氨基丙腈处理的细胞和对照细胞的全基因组表达谱显示，MC 3 T3-E1细胞的基质沉积提供了反馈信号，驱动细胞通过分化过程，当交联被抑制时，该信号被强烈削弱。抑制交联并不影响人间充质干细胞（hMSCs）的成骨分化，碱性磷酸酶的表达和全基因组基因表达分析显示，虽然它增强了基质矿化。总之，胶原交联在MC 3 T3-E1分化中具有指导性的性质，但在骨髓源性hMSCs的分化中起着更被动的作用。
Collagen is the main protein component of the extracellular matrix of bone, and it has structural and instructive properties. Collagen undergoes many post-translational modifications, including extensive crosslinking. Although defective crosslinking has been implicated in human syndromes (e.g., osteogenesis imperfecta or Ehlers-Danlos syndrome), it is not clear to what extent crosslinking is necessary for collagen's instructive properties during bone formation. Here we report that inhibition of collagen crosslinking in the mouse pre-osteoblast cell line MC3T3-E1 impairs the osteogenic program. Genome-wide expression profiling of beta-aminopropionitrile-treated and control cells revealed that matrix deposition by MC3T3-E1 cells provides a feed back signal, driving cells through the differentiation process, that is strongly impaired when crosslinking is inhibited. Inhibition of crosslinking did not affect osteogenic differentiation of human mesenchymal stem cells (hMSCs), shown by the expression of alkaline phosphatase and genome-wide gene expression analysis, although it enhances matrix mineralization. In conclusion, collagen crosslinking harbors instructive properties in MC3T3-E1 differentiation but plays a more-passive role in differentiation of bone marrow-derived hMSCs.