Mécanotransduction et cellules souches mésenchymateuses humaines : Etude de l'effet d'une contrainte d'étirement équibiaxial sur la voie de TGF-ß

Abstract : Transforming growth factor-ß (TGF-ß) is a key factor for chondrogenic differentiation of human mesenchymal stem cells (hMSCs). Mechanical loading has also been shown to be important in MSC differentiation, but mechanisms by which mechanotransduction occurs remain largely elusive. The aim of our work was to define the short-time effect of cyclic tensile strain (CTS, 0.5 Hz or 1 Hz, 5% equibiaxial strain) on the hMSCs. Firstly, we investigated the culture parameters for the isolation of hMSCs and by which the initial expansion was influenced. We chose the opitimal culture conditions for hMSCs. Secondly, we studied the effect of TGF-ß1 on the hMSCs and chondrocytes. We found that Smad3 phosphorylation (Smad3p) was increased after 1 hour by the stimulation of TGF-ß1, but decreased after 3 hours, Smad3p translocation to the nucleus was observed too, and the effect was dose-dependent. At the same time, TGF-ß1 increased the expression of the gene of Sox9. Finally, we studied the effect of CTS on the hMSCs and chondrocytes. Results showed that CTS had the same effect that TGF-ß1 on the Smad3 phosphorylation and the expression of the gene of Sox9: CTS increases the latent TGF-ß1 in the medium, increases the internalisation of the type II TGF-ß receptor and changes the form of hMSCs. Moreover a synergy effect between CTS and TGF-ß1 was observed. We conclude that CTS could stimulate MSC differentiation by the activation of endogenous TGF-ß signaling pathway. It seems that the mechanisms of mechanotransduction are controlled by multiple factors.
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Huahua Chen. Mécanotransduction et cellules souches mésenchymateuses humaines : Etude de l'effet d'une contrainte d'étirement équibiaxial sur la voie de TGF-ß. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10068⟩. ⟨tel-01748384⟩

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