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

Steven Vermeulen, Nadia Roumans, Floris Honig, Aurélie Carlier, Dennie G A J Hebels, Aysegul Dede Eren, Peter Ten Dijke, Aliaksei Vasilevich, Jan de Boer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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-β responsive gene, we investigated the link between mechanotransduction and TGF-β signaling. We discovered that mesenchymal stem cells exposed to both micro-topographies and TGF-β2 display synergistic induction of SMAD phosphorylation and transcription of the TGF-β target genes SCX, 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-β 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-β response. These findings provide novel insights into the convergence of mechanobiology and TGF-β signaling, which can lead to improved culture protocols and therapeutic applications.

Original languageEnglish
Article number120331
Number of pages14
JournalBiomaterials
Volume259
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Actin dynamics
  • Biomaterials
  • Mesenchymal stem cells
  • Scleraxis
  • Mechanobiology
  • TGF-beta
  • GROWTH-FACTOR-BETA
  • SERUM RESPONSE FACTOR
  • SMOOTH-MUSCLE ACTIN
  • PROTEIN-KINASE-C
  • BONE MORPHOGENETIC PROTEIN-2
  • TENOGENIC DIFFERENTIATION
  • GENE-EXPRESSION
  • MECHANICAL FORCE
  • MATRIX-STIFFNESS
  • MYOSIN-II

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