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Adipocyte-induced transdifferentiation of osteoblasts and its potential role in age-related bone loss

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  • Aline Clabaut, Universite du Littoral Cote d'Opal, Université de Lille
  • ,
  • Céline Grare, Universite du Littoral Cote d'Opal, Université de Lille
  • ,
  • Gaëlle Rolland-Valognes, Institut de Recherches Servier
  • ,
  • Jean Guillaume Letarouilly, Universite du Littoral Cote d'Opal, Université de Lille, CHU Lille
  • ,
  • Chantal Bourrier, Institut de Recherches Servier
  • ,
  • Thomas L. Andersen
  • Tanja Sikjær
  • Lars Rejnmark
  • Charlotte Ejersted, Syddansk Universitet
  • ,
  • Philippe Pastoureau, Institut de Recherches Servier
  • ,
  • Pierre Hardouin, Universite du Littoral Cote d'Opal, Université de Lille, CHU Lille
  • ,
  • Massimo Sabatini, Institut de Recherches Servier
  • ,
  • Odile Broux, Universite du Littoral Cote d'Opal, Université de Lille, CHU Lille

Our preliminary findings have lead us to propose bone marrow adipocyte secretions as new contributors to bone loss. Indeed, using a 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. In this study, microarray gene expression profiling showed profound transcriptomic changes in osteoblasts following coculture and confirmed the enrichment of the adipocyte gene signature. Double immunofluorescence microscopic analyses demonstrated the coexpression of adipogenic and osteoblastic specific markers in individual cells, providing evidence for a transdifferentiation event. At the molecular level, this conversion was associated with upregulated expression levels of reprogramming genes and a decrease in the DNA methylation level. In line with these in vitro results, preliminary immunohistochemical analysis of bone sections revealed adipogenic marker expression in osteoblasts from elderly subjects. Altogether, these data suggest that osteoblast transdifferentiation could contribute to decreased bone mass upon ageing.

TidsskriftPLOS ONE
StatusUdgivet - jan. 2021

Bibliografisk note

Publisher Copyright:
© 2021 Clabaut et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Copyright 2021 Elsevier B.V., All rights reserved.

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