Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Wnt signaling acts and is regulated in a human osteoblast differentiation dependent manner
AU - Eijken, M
AU - Meijer, I M J
AU - Westbroek, I
AU - Koedam, M
AU - Chiba, H
AU - Uitterlinden, A G
AU - Pols, H A P
AU - van Leeuwen, J P T M
N1 - Copyright 2008 Wiley-Liss, Inc.
PY - 2008/5/15
Y1 - 2008/5/15
N2 - The Wnt signaling pathway is an important regulator of cellular differentiation in a variety of cell types including osteoblasts. In this study, we investigated the impact of Wnt signaling on the function of human osteoblasts in relation to the stage of differentiation. Differentiating osteoblasts were created upon glucocorticoid (GC) treatment, whereas nondifferentiating osteoblasts were created by excluding GCs from the culture medium. GC-induced differentiation suppressed endogenous beta-catenin levels and transcriptional activity. During GC-induced osteoblast differentiation, activation of Wnt signaling slightly decreased alkaline phosphatase activity, but strongly suppressed matrix mineralization. In addition, mRNA expression of several Wnt signaling related genes was strongly regulated during GC-induced osteoblast differentiation, including frizzled homolog 8, dickkopf homolog 1, and secreted frizzled-related protein 1. In contrast, in the absence of GC-induced differentiation, Wnt signaling acted positively by stimulating basal alkaline phosphatase activity. Interestingly, pre-stimulation of Wnt signaling in early osteoblasts enhanced their differentiation capacity later on during the GC-induced differentiation process. In conclusion, we showed a differentiation-dependent effect of Wnt signaling on osteoblasts. Wnt signaling stimulated early osteoblasts in their capacity to differentiate, whereas mature osteoblasts were strongly inhibited in their capacity to induce mineralization. Moreover, osteoblast differentiation suppressed endogenous Wnt signaling and changed the expression of multiple Wnt signaling related genes.
AB - The Wnt signaling pathway is an important regulator of cellular differentiation in a variety of cell types including osteoblasts. In this study, we investigated the impact of Wnt signaling on the function of human osteoblasts in relation to the stage of differentiation. Differentiating osteoblasts were created upon glucocorticoid (GC) treatment, whereas nondifferentiating osteoblasts were created by excluding GCs from the culture medium. GC-induced differentiation suppressed endogenous beta-catenin levels and transcriptional activity. During GC-induced osteoblast differentiation, activation of Wnt signaling slightly decreased alkaline phosphatase activity, but strongly suppressed matrix mineralization. In addition, mRNA expression of several Wnt signaling related genes was strongly regulated during GC-induced osteoblast differentiation, including frizzled homolog 8, dickkopf homolog 1, and secreted frizzled-related protein 1. In contrast, in the absence of GC-induced differentiation, Wnt signaling acted positively by stimulating basal alkaline phosphatase activity. Interestingly, pre-stimulation of Wnt signaling in early osteoblasts enhanced their differentiation capacity later on during the GC-induced differentiation process. In conclusion, we showed a differentiation-dependent effect of Wnt signaling on osteoblasts. Wnt signaling stimulated early osteoblasts in their capacity to differentiate, whereas mature osteoblasts were strongly inhibited in their capacity to induce mineralization. Moreover, osteoblast differentiation suppressed endogenous Wnt signaling and changed the expression of multiple Wnt signaling related genes.
KW - Calcification, Physiologic
KW - Cell Differentiation/physiology
KW - Cell Line
KW - Glucocorticoids/pharmacology
KW - Humans
KW - Osteoblasts/cytology
KW - RNA, Messenger/analysis
KW - Signal Transduction/genetics
KW - Wnt Proteins/genetics
U2 - 10.1002/jcb.21651
DO - 10.1002/jcb.21651
M3 - Journal article
C2 - 18186078
VL - 104
SP - 568
EP - 579
JO - Journal of Cellular Biochemistry. Supplement
JF - Journal of Cellular Biochemistry. Supplement
SN - 0733-1959
IS - 2
ER -