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

TitleMT1-MMP-dependent control of skeletal stem cell commitment via a β1-integrin/YAP/TAZ signaling axis.
Publication TypeJournal Article
Year of Publication2013
AuthorsTang Y, R Rowe G, Botvinick EL, Kurup A, Putnam AJ, Seiki M, Weaver VM, Keller ET, Goldstein S, Dai J, Begun D, Saunders T, Weiss SJ
JournalDev Cell
Date Published2013 May 28
KeywordsAdaptor Proteins, Signal Transducing, Adipogenesis, Animals, Antigens, CD29, Bone Marrow Cells, Cell Lineage, Cell Nucleus, Cell Shape, Cells, Cultured, Chondrogenesis, Extracellular Matrix, Gene Knock-In Techniques, Humans, Matrix Metalloproteinase 14, Mesenchymal Stromal Cells, Mice, Mice, Inbred C57BL, Mice, Transgenic, Osteogenesis, Phenotype, Phosphoproteins, Proteolysis, Signal Transduction, Stem Cell Niche, Transcription Factors, Transcriptional Activation

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.

Alternate JournalDev. Cell
PubMed ID23685250
PubMed Central IDPMC3736823
Grant ListCA07169915 / CA / NCI NIH HHS / United States
P41 EB015890 / EB / NIBIB NIH HHS / United States
P60 DK020572 / DK / NIDDK NIH HHS / United States
R01 CA071699 / CA / NCI NIH HHS / United States
R01 CA138818 / CA / NCI NIH HHS / United States