Author:

Keywords:

Science & Technology, Technology, Engineering, Biomedical, Materials Science, Biomaterials, Engineering, Materials Science, 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, TGF-β, Actins, Cells, Cultured, Mechanotransduction, Cellular, Mesenchymal Stem Cells, Phosphorylation, Signal Transduction, Transforming Growth Factor beta, Biomedical Engineering

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.