Ex vivo human cellular models to study adipocyte-induced transdifferentiation of osteoblasts - Université du Littoral Côte d'Opale
Communication Dans Un Congrès Année : 2022

Ex vivo human cellular models to study adipocyte-induced transdifferentiation of osteoblasts

Résumé

Background : We previously showed, in a coculture model using human bone marrow stromal cells of commercial origine, that factors secreted by adipocytes induced the transdifferentiation of osteoblasts towards an adipocyte-like phenotype. Purpose : The goal of the research was to develop cellular models closer to the physiological environment, to confirm the theory of transdifferentiation in ageing and pathological conditions. Methods: Human femoral heads were collected during hip replacement surgery and processed to isolate (1) osteoblasts, with the spontaneous outgrowth method and (2) adipocytes, through collagenase treatment followed by ceiling and 2D culture. Results : (1) We used two rounds of outgrowth from trabecular bone fragments to isolate primary human cells. After osteogenic induction, the cells displayed a specific osteoblast phenotype, characterized by osteocalcin mRNA expression and mineralization. We could furthermore confirm the transdifferentiation of these primary osteoblasts following their incubation with conditioned medium from commercial adipocytes as evidenced by the increase in the levels of adipogenic mRNA markers (PPARG and HSD11B1, p<0.01, Leptin p<0.05). (2) Oil red O staining confirmed the isolation of fully-differentiated, mature primary adipocytes from bone biopsies. Preliminary analyses revealed that the secretome of these primary adipocytes induced osteoblast transdifferentiation in similar manner as the one from commercial adipocytes. Conclusions: Our new models based on primary cells isolated from bone biopsies confirmed the role played by adipocyte-secreted factors in the transdifferentiation of osteoblasts. In the future, we plan to compare inter-donor phenotype variations in relation to bone microarchitecture data obtained by X-ray microtomography. This will assess the existence of a correlation between the osteoblast response to adipocyte secretions and the quality of the bone from which the cells are derived.
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hal-04459334 , version 1 (15-02-2024)

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  • HAL Id : hal-04459334 , version 1

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Federica Quacquarelli, Damien Leterme, Aline Clabaut, Antonella Poloni, Odile Broux. Ex vivo human cellular models to study adipocyte-induced transdifferentiation of osteoblasts. 7th International meeting on Bone Marrow Adiposity, Sep 2022, Athens, Greece. ⟨hal-04459334⟩
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