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Dev Cell. 2013 May 28;25(4):402-16. doi: 10.1016/j.devcel.2013.04.011. Epub 2013 May 16.

MT1-MMP-dependent control of skeletal stem cell commitment via a β1-integrin/YAP/TAZ signaling axis.

Author information

1
Division of Molecular Medicine & Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

Abstract

In vitro, topographical and biophysical cues arising from the extracellular matrix (ECM) direct skeletal stem cell (SSC) commitment and differentiation. However, the mechanisms by which the SSC-ECM interface is regulated and the outcome of such interactions on stem cell fate in vivo remain unknown. Here we demonstrate that conditional deletion of the membrane-anchored metalloproteinase MT1-MMP (Mmp14) in mesenchymal progenitors, but not in committed osteoblasts, redirects SSC fate decisions from osteogenesis to adipo- and chondrogenesis. By effecting ECM remodeling, MT1-MMP regulates stem cell shape, thereby activating a β1-integrin/RhoGTPase signaling cascade and triggering the nuclear localization of the transcriptional coactivators YAP and TAZ, which serve to control SSC lineage commitment. These data identify a critical MT1-MMP/integrin/YAP/TAZ axis operative in the stem cell niche that oversees SSC fate determination.

PMID:
23685250
PMCID:
PMC3736823
DOI:
10.1016/j.devcel.2013.04.011
[Indexed for MEDLINE]
Free PMC Article

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