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bioRxiv · 10.1101/2020.01.13.903195

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

Vermeulen, S.·Roumans, N.·Honig, F.·Carlier, A.·Hebels, D. G.·Dede Eren, A.·ten Dijcke, P.·Vasilevich, A.·de Boer, J.
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Abstract

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.

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Vermeulen, S., Roumans, N., Honig, F., Carlier, A., Hebels, D. G., Dede Eren, A., ten Dijcke, P., Vasilevich, A., de Boer, J.. 2020-01-13. Surface topography is a context-dependent activator of TGF-β signaling in mesenchymal stem cells. https://doi.org/10.1101/2020.01.13.903195

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