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Communication Dans Un Congrès Année : 2019

SSC-derived adipocytes induce the transdifferentiation of osteoblasts into pre-adipocytes

Résumé

Our preliminary findings lead us to propose bone marrow adipocyte secretions as new actors of bone loss. Indeed using an in vitro coculture model based on human skeletal stem cells (SSCs), we previously showed that soluble factors secreted by adipocytes induced the conversion of osteoblasts towards an adipocyte-like phenotype. The aim of this study is to better characterize the changes triggered by the coculture and to strengthen our hypothesis of a transdifferentiation event. A gene expression kinetics performed to analyze the temporal changes in the osteoblast phenotype revealed that the conversion of osteoblasts is quickly initiated (from 9h of coculture) but still incomplete when compared to adipocytes. Transcriptomic analysis of 7 biological replicates demonstrated that osteoblasts presented different phenotypic changes according to the duration of coculture. In fact, 376 and 405 transcripts were significantly modified in cocultured osteoblasts compared with the monoculture controls upon 9h and 48h respectively. Gene ontology annotation analysis showed an enrichment in the adipocyte gene signature. In particular, we identified 24 genes which were associated with biological processes related to differentiation of adipocyte (2,1≤FC≥16,82). Double immunofluorescence microscopic analyses were performed to demonstrate the co-expression of adipogenic and osteoblastic proteins on a single cell level. The results clearly showed that at least 12% of the osteoblastic cells expressed the adipogenic marker PPARy2, when osteoblasts cells were incubated during only 48h with adipocyte conditioned medium. On molecular level, such conversion was associated with upregulated expression of specific reprogramming genes (p≤0.05). Moreover, whole genome methylation analyses showed that levels of 5-methylcytosine were strongly decreased (p≤0.01) in co-cultured osteoblasts, accompanied by an upregulation of TET1 gene expression (p≤0.05), an enzyme implicated in methylation. Taken together, these data show that osteoblast transdifferentiation is initiated rapidly and then progresses in a multi-step process.
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Dates et versions

hal-04459494 , version 1 (15-02-2024)

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  • HAL Id : hal-04459494 , version 1

Citer

Aline Clabaut, Céline Grare, Gaëlle Roland Valognes, Jean-Guillaume Letarouilly, Chantal Bourrier, et al.. SSC-derived adipocytes induce the transdifferentiation of osteoblasts into pre-adipocytes. 46th European Calcified Tissue Society Congress, May 2019, Budapest, Hungary. ⟨hal-04459494⟩
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