title: Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.
abstract: We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFβ3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sandy A
authors.initials: SA
authors.lastname: van Gool
authors.forename: Joyce A M
authors.initials: JA
authors.lastname: Emons
authors.forename: Jeroen C H
authors.initials: JC
authors.lastname: Leijten
authors.forename: Eva
authors.initials: E
authors.lastname: Decker
authors.forename: Carsten
authors.initials: C
authors.lastname: Sticht
authors.forename: Johannes C
authors.initials: JC
authors.lastname: van Houwelingen
authors.forename: Jelle J
authors.initials: JJ
authors.lastname: Goeman
authors.forename: Carin
authors.initials: C
authors.lastname: Kleijburg
authors.forename: Sicco A
authors.initials: SA
authors.lastname: Scherjon
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.forename: Jan Maarten
authors.initials: JM
authors.lastname: Wit
authors.forename: Gudrun
authors.initials: G
authors.lastname: Rappold
authors.forename: Janine N
authors.initials: JN
authors.lastname: Post
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
mesh_terms: D037881:Aborted Fetus / Q000166:cytology; D002356:Cartilage / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction; D059467:Transcriptome