Wnt signalling in mouse mesenchymal stem cells: Impact on proliferation, invasion and MMP expression
Karow M, Popp T, Egea V, Ries C, Jochum M, Neth P (2009)
Publication Type: Journal article
Publication year: 2009
Journal
Book Volume: 13
Pages Range: 2506-2520
Journal Issue: 8 B
DOI: 10.1111/j.1582-4934.2008.00619.x
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. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Involved external institutions
Germany (DE)How to cite
APA:
Karow, M., Popp, T., Egea, V., Ries, C., Jochum, M., & Neth, P. (2009). Wnt signalling in mouse mesenchymal stem cells: Impact on proliferation, invasion and MMP expression. Journal of Cellular and Molecular Medicine, 13(8 B), 2506-2520. https://doi.org/10.1111/j.1582-4934.2008.00619.x
MLA:
Karow, Marisa, et al. "Wnt signalling in mouse mesenchymal stem cells: Impact on proliferation, invasion and MMP expression." Journal of Cellular and Molecular Medicine 13.8 B (2009): 2506-2520.
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