title: Increased adipogenesis in cultured embryonic chondrocytes and in adult bone marrow of dominant negative Erg transgenic mice.
abstract: In monolayer culture, primary articular chondrocytes have an intrinsic tendency to lose their phenotype during expansion. The molecular events underlying this chondrocyte dedifferentiation are still largely unknown. Several transcription factors are important for chondrocyte differentiation. The Ets transcription factor family may be involved in skeletal development. One family member, the Erg gene, is mainly expressed during cartilage formation. To further investigate the potential role of Erg in the maintenance of the chondrocyte phenotype, we isolated and cultured chondrocytes from the rib cartilage of embryos of transgenic mice that express a dominant negative form of Erg (DN-Erg) during cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days did not affect the early dedifferentiation usually observed in cultured chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes, suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray, validated by quantitative RT-PCR, revealed strong differential gene expression, with a decrease in chondrogenesis-related markers and an increase in adipogenesis-related gene expression in cultured DN-Erg chondrocytes. These results indicate that Erg is involved in either maintaining the chondrogenic phenotype in vitro or in cell fate orientation. Along with the in vitro studies, we compared adipocyte presence in wild-type and transgenic mice skeletons. Histological investigations revealed an increase in the number of adipocytes in the bone marrow of adult DN-Erg mice even though no adipocytes were detected in embryonic cartilage or bone. These findings suggest that the Ets transcription factor family may contribute to the homeostatic balance in skeleton cell plasticity.
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Université de Lille Nord de France, Institut Pasteur de Lille/IFR142, Lille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Flajollet
authors.forename: Tian V
authors.initials: TV
authors.lastname: Tian
authors.forename: Ludovic
authors.initials: L
authors.lastname: Huot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Tomavo
authors.forename: Anne
authors.initials: A
authors.lastname: Flourens
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Marion
authors.initials: M
authors.lastname: Le Jeune
authors.forename: Patrick
authors.initials: P
authors.lastname: Dumont
authors.forename: David
authors.initials: D
authors.lastname: Hot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mallein-Gerin
authors.forename: Martine
authors.initials: M
authors.lastname: Duterque-Coquillaud
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism
chemical_list: C086924:Elk3 protein, mouse; D050783:Proto-Oncogene Proteins c-ets