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 language | English |
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Article number | 120331 |
Number of pages | 14 |
Journal | Biomaterials |
Volume | 259 |
DOIs | |
Publication status | Published - 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