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

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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Tang Y,Rowe RG,Botvinick EL,Kurup A,Putnam AJ,Seiki M,Weaver VM,Keller ET,Goldstein S,Dai J,Begun D,Saunders T,Weiss SJ

doi

10.1016/j.devcel.2013.04.011

subject

Has Abstract

pub_date

2013-05-28 00:00:00

pages

402-16

issue

4

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(13)00222-0

journal_volume

25

pub_type

杂志文章

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