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Extracellular matrix stiffness regulates osteogenic differentiation through MAPK activation

Title
Extracellular matrix stiffness regulates osteogenic differentiation through MAPK activation
Authors
HwangJ.-H.ByunM.R.KimA.R.K.M.ChoH.J.LeeY.H.J.JeongM.G.E.S.Hong
Ewha Authors
황은숙
SCOPUS Author ID
황은숙scopus
Issue Date
2015
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 10, no. 8
Publisher
Public Library of Science
Indexed
SCIE; SCOPUS WOS scopus
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.
DOI
10.1371/journal.pone.0135519
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약학대학 > 약학과 > Journal papers
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