title: Differentiation plasticity of chondrocytes derived from mouse embryonic stem cells.
abstract: Evidence exists that cells of mesenchymal origin show a differentiation plasticity that depends on their differentiation state. We used in vitro differentiation of embryonic stem cells through embryoid bodies as a model to analyze chondrogenic and osteogenic differentiation because embryonic stem cells recapitulate early embryonic developmental phases during in vitro differentiation. Here, we show that embryonic stem cells differentiate into chondrocytes, which progressively develop into hypertrophic and calcifying cells. At a terminal differentiation stage, cells expressing an osteoblast-like phenotype appeared either by transdifferentiation from hypertrophic chondrocytes or directly from osteoblast precursor cells. Chondrocytes isolated from embryoid bodies initially dedifferentiated in culture but later re-expressed characteristics of mature chondrocytes. The process of redifferentiation was completely inhibited by transforming growth factor beta3. In clonal cultures of chondrocytes isolated from embryoid bodies, additional mesenchymal cell types expressing adipogenic properties were observed, which suggests that the subcultured chondrocytes indeed exhibit a certain differentiation plasticity. The clonal analysis confirmed that the chondrogenic cells change their developmental fate at least into the adipogenic lineage. In conclusion, we show that chondrocytic cells are able to transdifferentiate into other mesenchymal cells such as osteogenic and adipogenic cell types. These findings further strengthen the view that standardized selection strategies will be necessary to obtain defined cell populations for therapeutic applications.
authors.affiliation: Department of Medical Molecular Biology, Medical University of Lübeck, D-23538 Lübeck, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hegert
authors.forename: Jan
authors.initials: J
authors.lastname: Kramer
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hargus
authors.forename: Jana
authors.initials: J
authors.lastname: Müller
authors.forename: Kaomei
authors.initials: K
authors.lastname: Guan
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wobus
authors.forename: Peter K
authors.initials: PK
authors.lastname: Müller
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rohwedel
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D006984:Hypertrophy; D017404:In Situ Hybridization, Fluorescence; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053782:Transforming Growth Factor beta3
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D024121:Collagen Type X; D012333:RNA, Messenger; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3