TY - JOUR
T1 - The role of collagen crosslinking in differentiation of human mesenchymal stem cells and MC3T3-E1 cells
AU - Fernandes, Hugo
AU - Dechering, Koen
AU - van Someren, Eugene
AU - Steeghs, Ilse
AU - Apotheker, Marion
AU - Leusink, Anouk
AU - Bank, Ruud
AU - Janeczek, Karolina
AU - van Blitterswijk, Clemens
AU - de Boer, Jan
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=72049100698&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2009.0011
DO - 10.1089/ten.tea.2009.0011
M3 - Article
AN - SCOPUS:72049100698
SN - 1937-3341
VL - 15
SP - 3857
EP - 3867
JO - Tissue engineering. Part A
JF - Tissue engineering. Part A
IS - 12
ER -