PhD defense Anne VALAT

Involvement and Regulation of integrins and cadherins in the BMP-2-induced Muscle/Bone transdifferentiation: biomimetic approach

Thèse de Anne VALAT

Keywords :Différenciation – BMP-2 – Intégrine – Cadhérine – Biomatériau – Muscle – Os 

Directeur de thèse : Prof; C.PICART - Grenoble INP, LMGP, équipe IMBM et Dr C.ALBIGES RIZO - CNRS - IAB La Tronche

click here to see the jury members


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 b3 and BMP receptors in the induction of cell spreading and of an early response to BMP-2 via the protein GSK3b. 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 b3 and b5 integrins and cadherins N and 11 for the BMP-2-induced transdifferentiation.


Jury members :
Prof. MH Lafage Proust - SAINBIOSE (SAnté INgénierie BIOlogie St-Etienne), ISERM - St Priest-en-Jarez - France - rapporteur
Dr C.Gauthier Rouvière - CRBM, CNRS Montpellier - France - Rapporteur
Dr RM Mège - Institut Jacques Monod, CNRS - Paris - France - Examinateur
Prof L.Schaeffer - Ens de Lyon - Lyon - France - Examinateur
Prof F Luyten - Skemetam Biology and Engineering Research Center - Leuven - Belgique - Examinateur
Prof F.Bruckert - LMGP, CNRS, Grenoble INP Minatec, Grenoble - France - Président du jury
Dr C. Albigès Rizo - IAB - CNRS - La Tronche - France - Co-Directeur de thèse
Prof C. Picart - LMGP - CNRS - Grenoble INP Minatec - Grenoble - France -Directeur de thèse

Date infos
3:00 pm- M001 - Ground Floor - PHELMA - MINATEC
Location infos
Grenoble INP - Phelma
3 parvis Louis Néel - 38000 Grenoble
Accès : TRAM B arrêt Cité internationale
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