Title | MT1-MMP-dependent control of skeletal stem cell commitment via a β1-integrin/YAP/TAZ signaling axis. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Tang 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 |
Journal | Dev Cell |
Volume | 25 |
Issue | 4 |
Pagination | 402-16 |
Date Published | 2013 May 28 |
ISSN | 1878-1551 |
Keywords | Adaptor 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 |
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. |
DOI | 10.1016/j.devcel.2013.04.011 |
Alternate Journal | Dev. Cell |
PubMed ID | 23685250 |
PubMed Central ID | PMC3736823 |
Grant List | CA07169915 / 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 |