Matrix stiffness regulates the differentiation of tendon-derived stem cells through FAK-ERK1/2 activation
| Autor: | Jing-Wan Luo, Ting Liang, Yu Long Sun, Long-Xiang Lin, Chang Liu, Zong-ping Luo, Yong-Qing Zhuang |
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| Rok vydání: | 2018 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine animal structures Cell Survival MAP Kinase Signaling System macromolecular substances 02 engineering and technology Biology Matrix (biology) Chondrocyte Rats Sprague-Dawley Tendons 03 medical and health sciences Western blot medicine Animals Cell Proliferation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 medicine.diagnostic_test Stem Cells technology industry and agriculture Cell Differentiation Hydrogels Cell Biology musculoskeletal system 021001 nanoscience & nanotechnology Chondrogenesis Cell biology RUNX2 Enzyme Activation Actin Cytoskeleton 030104 developmental biology medicine.anatomical_structure Osteocyte Focal Adhesion Kinase 1 Self-healing hydrogels Gelatin Stem cell 0210 nano-technology |
| Zdroj: | Experimental cell research. 373(1-2) |
| ISSN: | 1090-2422 |
| Popis: | 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 ± 1.48 kPa to 24.09 ± 14.03 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. |
| Databáze: | OpenAIRE |
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