Matrix stiffness regulates the differentiation of tendon-derived stem cells through FAK-ERK1/2 activation.
Exp Cell Res
; 373(1-2): 62-70, 2018 12 15.
Article
em En
| MEDLINE
| ID: mdl-30138615
ABSTRACT
Tendon derived stem cells (TDSCs) were vital in tendon homeostasis. Nevertheless, the regulation of TDSCs differentiation in tendinopathy is unclear. Matrix stiffness modulated stem cells differentiation, and matrix stiffness of tendinopathic tissues decreased significantly. In order to clarify the role of matrix stiffness in TDSCs differentiation, they were cultured on the gelatin hydrogels with the stiffness from 2.34⯱â¯1.48â¯kPa to 24.09⯱â¯14.03â¯kPa. The effect of matrix stiffness on TDSCs proliferation and differentiation were investigated with CCK8 assay, immunofluorescences, real time PCR and western blot. It was found the proliferation of TDSCs increased and more stress fibers formed with increasing matrix stiffness. The differentiation of TDSCs into tenogenic, chondrogenic, and osteogenic lineages were inhibited on stiff hydrogel evidenced by reduced expression of tenocyte markers THBS4, TNMD, SCX, chondrocyte marker COL2, and osteocyte markers Runx2, Osterix, and ALP. Furthermore, the phosphorylation of FAK and ERK1/2 were enhanced when TDSCs grew on stiff hydrogel. After FAK or ERK1/2 was inhibited, the effect of matrix stiffness on differentiation of TDSCs was inhibited as well. The above results indicated matrix stiffness modulated the proliferation and differentiation of TDSCs, and the regulation effect could correlate to the activation of FAK or ERK1/2.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Tendões
/
Diferenciação Celular
/
Proteína Quinase 1 Ativada por Mitógeno
/
Proteína Quinase 3 Ativada por Mitógeno
/
Quinase 1 de Adesão Focal
Limite:
Animals
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2018
Tipo de documento:
Article