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Dede Eren, A.

Publications and source records attributed to Dede Eren, A..

2 recordsLinked to original sources

Tendon-derived biomimetic surface topographies induce phenotypic maintenance of tenocytes in vitro

The tenocyte niche contains biochemical and biophysical signals that are needed for tendon homeostasis. The tenocyte phenotype is correlated with cell shape in vivo and in vitro, and shape-modifying cues are needed for tenocyte phenotypical maintenance. Indeed, cell shape changes from elongated to spread when cultured on a flat surface, and rat tenocytes lose the expression of phenotypical markers throughout five passages. We hypothesized that tendon gene expression can be preserved by culturing cells in the native tendon shape. To this end, we reproduced the tendon topographical landscape into tissue culture polystyrene, using imprinting technology. We confirmed that the imprints forced the cells into a more elongated shape, which correlated with the level of Scleraxis expression. When we cultured the tenocytes for seven days on flat surfaces and tendon imprints, we observed a decline in tenogenic marker expression on flat but not on imprints. This research demonstrates that native tendon topography is an important factor contributing to the tenocyte phenotype. Tendon imprints therefore provide a powerful platform to explore the effect of instructive cues originating from native tendon topography on guiding cell shape, phenotype and function of tendon-related cells.

bioengineering↗

Surface topography is a context-dependent activator of TGF-β signaling in mesenchymal stem cells

We previously found that surface topographies induce the expression of the Scxa gene, encoding Scleraxis in tenocytes. Because Scxa is a TGF-{beta} responsive gene, we investigated the link between mechanotransduction and TGF-{beta} signaling. We discovered that mesenchymal stem cells exposed to both micro-topographies and TGF-{beta}2 display synergistic induction of SMAD phosphorylation and transcription of the TGF-{beta} target genes SCXA, a-SMA, and SOX9. Pharmacological perturbations revealed that Rho/ROCK/SRF signaling is required for this synergistic response. We further found an activation of the early response genes SRF and EGR1 during the early adaptation phase on micro-topographies, which coincided with higher expression of the TGF-{beta} type-II receptor gene. Of interest, PKC activators Prostratin and Ingenol-3, known for inducing actin reorganization and activation of serum response elements, were able to mimic the topography-induced TGF-{beta} response. These findings provide novel insights into the convergence of mechanobiology and TGF-{beta} signaling, which can lead to improved culture protocols and therapeutic applications.

cell biology↗