Effect of chordin-like 1 on MC3T3-E1 and human mesenchymal stem cells.
Since the discovery that bone morphogenetic proteins (BMPs) are able to induce ectopic bone formation, considerable effort has been devoted to apply it for bone regeneration. BMP activity needs to be temporally and spatially controlled and the organism has devised ways to achieve it. Here we show that the BMP inhibitor chordin-like 1 can interfere with BMP2 signalling thereby affecting the osteogenic differentiation of MC3T3-E1 cells. Besides its function as a BMP antagonist, chordin-like 1 enhanced the proliferation of human mesenchymal stem cells (hMSCs) in a BMP2-independent manner. When MC3T3-E1 cells were exposed to recombinant chordin-like 1 there was an inhibition of alkaline phosphatase (ALP) expression, whereas in the case of hMSCs no effect was observed. However, chordin-like 1 dose-dependently increased the proliferation of hMSCs. This effect is probably BMP2 independent because the chordin-like 1 concentration that stimulates proliferation does not interfere with BMP signalling monitored by a Smad-dependent reporter gene. Our data point towards a novel, BMP-independent role of chordin-like 1 in hMSC proliferation.
Department of Tissue Regeneration, University of Twente, Enschede, The Netherlands.
Hugo
H
Fernandes
Koen
K
Dechering
Eugene
E
van Someren
Ilse
I
Steeghs
Marion
M
Apotheker
Anouk
A
Mentink
Clemens
C
van Blitterswijk
Jan
J
de Boer
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics
D055396:Bone Morphogenetic Protein 2; C430597:Chrdl1 protein, mouse; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D000469:Alkaline Phosphatase