• Open Access

Wnt signalling in mouse mesenchymal stem cells: impact on proliferation, invasion and MMP expression

Authors

  • Marisa Karow,

    1. Division of Clinical Chemistry and Clinical Biochemistry, Department of Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
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  • Tanja Popp,

    1. Division of Clinical Chemistry and Clinical Biochemistry, Department of Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
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  • Virginia Egea,

    1. Division of Clinical Chemistry and Clinical Biochemistry, Department of Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
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  • Christian Ries,

    1. Division of Clinical Chemistry and Clinical Biochemistry, Department of Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
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  • Marianne Jochum,

    1. Division of Clinical Chemistry and Clinical Biochemistry, Department of Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
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  • Peter Neth

    Corresponding author
    1. Division of Clinical Chemistry and Clinical Biochemistry, Department of Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
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Correspondence to: Peter NETH, Ph.D., Abteilung für Klinische Chemie und Klinische Biochemie, Chirurgische Klinik und Poliklinik – Innenstadt, Nussbaumstr. 20, 80336 München, Germany.
Tel.: +49-89-5160-2530
Fax: +49-89-5160-4740
E-mail: peter.neth@med.uni-muenchen.de

Abstract

Based on the capacity of mesenchymal stem cells (MSC) to differentiate into multiple cell types in vitro and in vivo, MCS may be a suitable source for cell therapy and regeneration strategies. A prerequisite for effective clinical applications of human MSC (hMSC) is a profound knowledge of signal transduction cascades that mediate processes like proliferation, targeted migration and differentiation. Recently, we identified the canonical Wnt signal transduction pathway as a key player in hMSC proliferation and invasion. To evaluate whether those findings are transferable to the equivalent counterparts in mice, we studied important steps in the wingless/int-1 (Wnt) signal transduction pathway in mouse MSC (mMSC) and mMSC carrying a T cell specific transcription factor (TCF)/lymphoid enhancer binding factor (LEF)-reporter transgene. We found that the induction of the canonical Wnt pathway resulted in the up-regulation of the known Wnt target gene cyclin D1, closely associated with an enhanced proliferation capacity of mMSC. Interestingly, the expression of the Wnt target gene membrane type 1-matrix metalloproteinase (MT1-MMP) was diminished in mMSC upon Wnt3a stimulation, which came along with an impaired invasion. In line with these findings, MMP-2 and MMP-9 expression levels in mMSC were also decreased after Wnt3a treatment. In contrast, inhibition of Wnt signalling by the knockdown of the transcriptional activator β-catenin resulted in an up-regulation of MT1-MMP and mMSC invasion. By comparing these findings with the settings in hMSC, major differences in Wnt-regulated MMP expression were observed in mMSC. Thus, our data advice caution when mouse model systems represent the pre-clinical validation of MSC-mediated therapeutical approaches.

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