MT1-MMP-Dependent Control of Skeletal Stem Cell Commitment via a β1-Integrin/YAP/TAZ Signaling Axis
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説明
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.
収録刊行物
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- Developmental Cell
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Developmental Cell 25 (4), 402-416, 2013-05
Elsevier BV
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キーワード
- Transcriptional Activation
- Cells
- Bone Marrow Cells
- Cell Cycle Proteins
- Mice, Transgenic
- Regenerative Medicine
- Inbred C57BL
- Medical and Health Sciences
- Transgenic
- Mice
- Rare Diseases
- Osteogenesis
- Matrix Metalloproteinase 14
- 2.1 Biological and endogenous factors
- Animals
- Humans
- Cell Lineage
- Gene Knock-In Techniques
- Aetiology
- Stem Cell Niche
- Cell Shape
- Cells, Cultured
- Adaptor Proteins, Signal Transducing
- Cell Nucleus
- Cultured
- Adipogenesis
- Integrin beta1
- Signal Transducing
- Adaptor Proteins
- Mesenchymal Stem Cells
- YAP-Signaling Proteins
- Biological Sciences
- Stem Cell Research
- Phosphoproteins
- Extracellular Matrix
- Mice, Inbred C57BL
- Phenotype
- Biochemistry and cell biology
- Proteolysis
- Stem Cell Research - Nonembryonic - Non-Human
- Biochemistry and Cell Biology
- Chondrogenesis
- Acyltransferases
- Developmental Biology
- Signal Transduction
- Transcription Factors
詳細情報 詳細情報について
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- CRID
- 1360283690865092864
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- ISSN
- 15345807
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- PubMed
- 23725758
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
