Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.
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.
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Jun-Ha
JH
Hwang
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Mi Ran
MR
Byun
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
A Rum
AR
Kim
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Kyung Min
KM
Kim
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Hang Jun
HJ
Cho
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Yo Han
YH
Lee
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Juwon
J
Kim
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Mi Gyeong
MG
Jeong
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Eun Sook
ES
Hwang
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Jeong-Ho
JH
Hong
D000199:Actins / Q000378:metabolism; D000217:Acyltransferases; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology; D002454:Cell Differentiation; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D010641:Phenotype; D021381:Protein Transport; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D054460:rho-Associated Kinases / Q000378:metabolism
D000199:Actins; D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D054460:rho-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases