Abstract
Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Acyltransferases
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Adipocytes / cytology
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Adipocytes / metabolism
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Adipogenesis / physiology
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Cell Differentiation*
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Enzyme Activation
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Extracellular Matrix / metabolism*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Mesenchymal Stem Cells / cytology
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Mesenchymal Stem Cells / metabolism
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Mitogen-Activated Protein Kinases / metabolism*
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Models, Biological
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Osteoblasts / cytology
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Osteoblasts / metabolism
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Osteogenesis / physiology*
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Phenotype
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Protein Transport
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Signal Transduction
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Transcription Factors / metabolism
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Transcriptional Activation
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rho-Associated Kinases / metabolism
Substances
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Actins
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Transcription Factors
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Acyltransferases
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TAFAZZIN protein, human
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rho-Associated Kinases
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
Grants and funding
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant nos. 2014R1A2A2A01006547 and 2014R1A1A2057408) and by a grant from the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry for Health & Welfare (grant no. HI14C3266), Republic of Korea. This work was also supported by a grant from Korea University.