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Communication Dans Un Congrès Année : 2021

A multiomics approach to decipher adipocyte-induced transdifferentiation of osteoblast

Résumé

Background: Our preliminary findings lead us to propose bone marrow adipocyte secretions as new contributors to bone loss. Indeed using an in vitro coculture model based on human bone marrow stromal cells, we previously showed that soluble factors secreted by adipocytes induced the conversion of osteoblasts towards an adipocyte-like phenotype. This change in fate was confirmed by microarray gene expression profiling showing an enrichment in the adipocyte gene signature in cocultured osteoblasts. Furthermore double immunofluorescence staining demonstrated the co-expression of adipogenic and osteoblast specific markers in individual cells, providing evidence for a transdifferentiation event. Purpose: The aim of this study was to identify adipocyte-secreted factor(s) implicated in the transdifferentiation of osteoblasts into adipocyte-like cells, and the molecular mechanisms underlying their actions. Methods: One dimensional LC-MS/MS and label-free quantification were used to compare stimulatory and non-stimulatory adipocyte culture supernatants and identify a set of adipocyte-secreted proteins potentially regulators of osteoblast differentiation. In parallel, gene expression changes induced by adipocyte secretion products in the osteoblastic cells were identified by transcriptional analysis at two early stages of coculture. Physical interactions between adipocyte secreted proteins and osteoblast membrane protein coding genes were then investigated using data from StringDB. Results: The network of interactions consisted of 92 adipocyte-secreted proteins interacting with 454 osteoblast membrane protein coding genes, for a total of 271 predicted physical interactions. By linking these results with genes whose expression was subsequently modified in cells, we identified potential pathways affected by the coculture. For the validation of our approach, we focused on some of them, including TGF-beta/Smad and PI3K/AKT signalling pathways, of particular interest in the balance between osteogenesis and adipogenesis. Conclusions: Our findings provide new insights into the crosstalk between adipocytes and osteoblasts in the bone marrow and demonstrate the powerfulness of our integrative omics strategy to decipher cell-cell communication events.
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Dates et versions

hal-04459254 , version 1 (15-02-2024)

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  • HAL Id : hal-04459254 , version 1

Citer

Federica Quacquarelli, Ayyoub Salmi, Christophe Chauveau, Aline Clabaut, Odile Broux. A multiomics approach to decipher adipocyte-induced transdifferentiation of osteoblast. European Calcified Tissue Society Meeting, May 2021, Brussels, Belgium. ⟨hal-04459254⟩
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