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Rôle et régulation des intégrines et des cadhérines dans la transdifférenciation MUSCLE/OS en réponse à la BMP-2 : approche biomimétique

Abstract : Muscle and bone cooperate both mechanically and biochemically, through growth factors and cytokines. Following a bone lesion, stem cells are recruited and their differentiation is induced via the secretion of bioactive molecules such as growth factors. One strategy in bone tissue engineering is to combine materials with bone growth factors. Bone Morphogenetic Proteins (BMPs), which can be presented to the cell either in solution or bound to the matrix, belong to the basic growth factor family and play a very important role in bone formation. BMPs induce not only the differentiation of bone progenitors, but also the transdifferentiation of muscle progenitors towards an osteoblastic phenotype. Obtaining the complexity of the bone tissue architecture requires continuous interactions between the cell and its microenvironment. These interactions are mediated by cell/matrix and cell/cell receptors (integrins and cadherins, respectively). In this thesis, we investigated the role of the adhesion system in the context of its response to BMP-2 during the transdifferentiation of C2C12 murine myoblasts. To do so, we used polelectrolyte multilayer films composed of hyaluronan and poly(L-lysine) as a biomaterial to present BMP-2 in a matrix-bound manner. Short term, we revealed a cooperation between the integrin 3 and BMP receptors in the induction of cell spreading and of an early response to BMP-2 via the protein GSK3. In a longer term, we showed a switch in the repertoire of adhesion receptors in response to BMP-2. Finally, our results suggest a cooperation between 3 and 5 integrins and cadherins N and 11 for the BMP-2-induced transdifferentiation.
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https://tel.archives-ouvertes.fr/tel-01865839
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Submitted on : Sunday, September 2, 2018 - 1:17:55 AM
Last modification on : Monday, July 20, 2020 - 10:06:04 AM
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Anne Valat. Rôle et régulation des intégrines et des cadhérines dans la transdifférenciation MUSCLE/OS en réponse à la BMP-2 : approche biomimétique. Biomécanique [physics.med-ph]. Université Grenoble Alpes, 2016. Français. ⟨NNT : 2016GREAI045⟩. ⟨tel-01865839⟩

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