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Enhanced osteogenic differentiation of MC3T3‐E1 cells on grid‐topographic surface and evidence for involvement of YAP mediator
Author(s) -
Zhang Yingying,
Gong He,
Sun Yan,
Huang Yan,
Fan Yubo
Publication year - 2016
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35648
Subject(s) - extracellular matrix , microbiology and biotechnology , cellular differentiation , gene knockdown , cell , materials science , transcription factor , extracellular , runx2 , intracellular , alkaline phosphatase , cell fate determination , biology , cell culture , biochemistry , enzyme , gene , genetics
Numerous studies have shown that surface topography can promote cell–substrate associations and deeply influence cell fate. The intracellular mechanism or how micro‐ or nano‐patterned extracellular signal is ultimately linked to activity of nuclear transcription factors remains unknown. It has been reported that Yes‐associated protein (YAP) can respond to extracellular matrix microenvironment signals, thus regulates stem cell differentiation process. We propose that YAP may play a role in mediating the topography induced cell differentiation. To this end, we fabricated polydimethylsiloxane (PDMS) micropatterns with grid topology (GT) (3 μm pattern width, 2 μm pattern interval length, 7 μm pattern height); nonpatterned PDMS substrates were used as the planar controls. The MC3T3‐E1 cells were then cultured on these surfaces, respectively, in osteogenic inducing medium. Cell differentiation in terms of osteogenesis related gene expression, protein levels, alkaline phosphatase activity and extracellular matrix mineralization was assessed. It was shown that the cells on GT surfaces had stronger osteogenesis capacity. In addition, expression level of YAP was increased when MC3T3‐E1 cells grew on GT substrates, which was similar to the levels of osteogenic differentiation markers. It was also shown that YAP knockdown attenuated GT substrates‐induced MC3T3‐E1 differentiation, which reduced the osteogenic differentiation effect of the GT substrates. Collectively, our findings indicate that GT substrates‐induced MC3T3‐E1 differentiation may be associated with YAP. This paper provides new target points for transcriptional mechanism research of microenvironment induced cell differentiation and a useful approach to obtain more biofunctionalization scaffolds for tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1143–1152, 2016.