title: The role of collagen crosslinking in differentiation of human mesenchymal stem cells and MC3T3-E1 cells.
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.
authors.affiliation: Department of Tissue Regeneration, University of Twente, Enschede, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fernandes
authors.forename: Koen
authors.initials: K
authors.lastname: Dechering
authors.forename: Eugene
authors.initials: E
authors.lastname: Van Someren
authors.forename: Ilse
authors.initials: I
authors.lastname: Steeghs
authors.forename: Marion
authors.initials: M
authors.lastname: Apotheker
authors.forename: Anouk
authors.initials: A
authors.lastname: Leusink
authors.forename: Ruud
authors.initials: R
authors.lastname: Bank
authors.forename: Karolina
authors.initials: K
authors.lastname: Janeczek
authors.forename: Clemens
authors.initials: C
authors.lastname: Van Blitterswijk
authors.forename: Jan
authors.initials: J
authors.lastname: de Boer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors
chemical_list: D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase