RRC ID 12447
Author Fernandes H, Dechering K, Van Someren E, Steeghs I, Apotheker M, Leusink A, Bank R, Janeczek K, Van Blitterswijk C, de Boer J.
Title The role of collagen crosslinking in differentiation of human mesenchymal stem cells and MC3T3-E1 cells.
Journal Tissue Eng Part A
Abstract 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.
Volume 15(12)
Pages 3857-67
Published 2009-12-1
DOI 10.1089/ten.tea.2009.0011
PMID 19694522
MeSH Animals Cell Differentiation* / drug effects Collagen / metabolism* Cross-Linking Reagents / metabolism* Enzyme Inhibitors / pharmacology Extracellular Matrix / drug effects Extracellular Matrix / genetics Gene Expression Profiling Gene Expression Regulation / drug effects Humans Mesenchymal Stem Cells / cytology* Mesenchymal Stem Cells / drug effects Mesenchymal Stem Cells / enzymology Mesenchymal Stem Cells / metabolism* Mice Models, Biological Osteoblasts / cytology* Osteoblasts / drug effects Osteoblasts / enzymology Osteoblasts / metabolism* Osteogenesis / drug effects Protein-Lysine 6-Oxidase / antagonists & inhibitors
IF 3.508
Times Cited 35
Human and Animal Cells MC3T3-E1(RCB1126)