Interplay between integrins and cadherins to control bone differentiation upon BMP-2 stimulation

• DOI: 10.3389/fcell.2022.1027334
• Publication Date: 2023-01-04T15:14:41Z
• Authors: Anne Valat; Laure Fourel; Adria Sales; Paul Machillot; Anne-Pascale Bouin; Carole Fournier; Lauriane Bosc; Mélanie Arboléas; Ingrid Bourrin-Re...; Amy J. Wagoner Jo...; Franz Bruckert; Corinne Albigès-Rizo; Catherine Picart
• Keywords: C2C12; Transdifferentiation; RUNX2

Introduction: Upon BMP-2 stimulation, the osteoblastic lineage commitment in C2C12 myoblasts is associated with a microenvironmental change that occurs over several days. How does operate switch adhesive machinery to adapt new microenvironment and drive bone cell fate not well understood. Here, we addressed this question for delivered either solution or physically bound of biomimetic film, mimic its presentation cells via extracellular matrix (ECM). Methods: Biommetics films were prepared using recently developed automated method enable high content studies cellular processes. Comparative gene expressions done RNA sequencing from encyclopedia regulatory elements (ENCODE). Gene transcription factors, beta chain (1, 3, 5) integrins cadherins (M, N, Cad11) studied quantitative PCR. ECM proteins adhesion receptor also quantified by Western blots dot blots. Their spatial organization around was immuno-stainings. The individual effect each on osteogenic factors alkaline phosphatase expression silencing integrin cadherin receptor. fibronectin immuno-staining microscopic analysis. Results: Our findings highlight during muscle transdifferentiation upon stimulation. This no matter mode, presented film. While express M-cadherin Laminin-specific integrins, BMP-2-induced into an increase cadherin-11 collagen-specific integrins. Biomimetic presenting matrix-bound revelation specific roles receptors depending factor. Discussion: β3 work concert control early pSMAD1,5,9 signaling, β1 Cadherin-11 RunX2, ALP activity cells. In contrast, while important osterix transcriptional activity, β5 act as negative regulators. addition, negatively regulates RunX2. results show can be used delinate events BMP-2-mediated transdifferentiation. study reveals how together, exerting distinct functions programming. Different sets have complementary mechanical time window