Accessible Requires Authentication Published by De Gruyter November 13, 2012

Dissecting the impact of Frizzled receptors in Wnt/β-catenin signaling of human mesenchymal stem cells

Thomas Kolben, Iris Peröbner, Katharina Fernsebner, Felix Lechner, Claudia Geissler, Lourdes Ruiz-Heinrich, Simon Capovilla, Marianne Jochum and Peter Neth
From the journal Biological Chemistry

Abstract

Wnt/β-catenin signaling is of fundamental importance in the regulation of self-renewal, migration/invasion, and differentiation of human mesenchymal stem cells (hMSCs). Because little information is available about the function of Frizzled receptors (Fzds) as the main receptors of Wnt proteins in hMSCs, we first performed comparative Fzd mRNA expression profiling. Fzd9 and Fzd10 were not expressed in hMSCs. While Fzd3 was expressed at low levels in hMSCs, the other Fzds exhibited high expression rates. Activation and repression of Wnt signaling in hMSCs revealed that the expression levels of Fzd1, Fzd6, and Fzd7 are positively correlated with the Wnt/β-catenin activation status, whereas Fzd8 exhibited an inverse relation. For studying the functional relevance of Fzds in Wnt/β-catenin signaling, RNA interference, ectopic expression studies, and rescue approaches were performed in hMSCs carrying a highly sensitive TCF/LEF reporter gene system (Gaussia luciferase). We found that, Fzd1, Fzd5, Fzd7, and Fzd8 are largely involved in Wnt/β-catenin signaling of hMSCs. Moreover, the knockdown of Fzd5 can be compensated by the ectopic expression of Fzd7. Conversely, the ectopic expression of Fzd5 in Fzd7-knockdown hMSCs resulted in a rescue of Wnt/β-catenin signaling, pointing to a functional redundancy of Fzd5 and Fzd7.


Corresponding author: Peter Neth, Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University, Pettenkoferstr. 9a, 80336 Munich, Germany

Received: 2012-4-26
Accepted: 2012-9-24
Published Online: 2012-11-13
Published in Print: 2012-12-01

©2012 by Walter de Gruyter Berlin Boston