To obtain a cell source for cartilage tissue engineering primary cells are passaged on polystyrene dishes to increase cell number however, this stiff environment results in dedifferentiation. This study evaluates the role of microenvironment stiffness on regulation of passaged chondrocyte phenotype. Results show passaged cells on soft polyacrylamide gels (0.5kPa) become round, less proliferative, less contractile, have higher levels of globular actin (g-actin) compared to filamentous actin (f-actin), MRTF localization in the cytoplasm and down-regulation of MRTF associated genes such as type I collagen, alpha-smooth muscle actin, transgelin, tenascin C and vinculin. This suggests that the chondrogenic phenotype during passaging is regulated by actin polymerization and activation of MRTF signaling that induces expression of non-chondrogenic genes, and has functional effects as the cells become proliferative and contractile. Modulating substrate stiffness maybe a way to influence aspects of the chondrogenic phenotype in order to obtain sufficient cells suitable for cartilage tissue engineering.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/65591 |
| Date | 03 July 2014 |
| Creators | Nabavi Niaki, Mortah |
| Contributors | Kandel, Rita |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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