TY - JOUR
T1 - Adipocyte-induced transdifferentiation of osteoblasts and its potential role in age-related bone loss
AU - Clabaut, Aline
AU - Grare, Céline
AU - Rolland-Valognes, Gaëlle
AU - Letarouilly, Jean-Guillaume
AU - Bourrier, Chantal
AU - Levin Andersen, Thomas
AU - Sikjær, Tanja Tvistholm
AU - Rejnmark, Lars
AU - Ejersted, Charlotte Albjerg
AU - Pastoureau, Philippe
AU - Hardouin, Pierre
AU - Sabatini, Massimo
AU - Broux, Odile
N1 - Funding: CentEx Biotechnology provided support for this study in the form of salaries for GRV and CB. The specific roles of these authors are articulated in the ‘author contributions’ section. The funder participated in study design, data collection and analysis, and preparation of the manuscript, but did not have a role in the decision to publish the manuscript.
PY - 2021/1/26
Y1 - 2021/1/26
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0245014
DO - 10.1371/journal.pone.0245014
M3 - Journal article
C2 - 33497412
SN - 1932-6203
VL - 16
JO - PLOS ONE
JF - PLOS ONE
IS - 1
M1 - e0245014
ER -