title: Gene expression profile of multipotent mesenchymal stromal cells: Identification of pathways common to TGFbeta3/BMP2-induced chondrogenesis.
abstract: Multipotent mesenchymal stromal cells (MSC) display a high potential for the development of novel treatment strategies for cartilage repair. However, the pathways involved in their differentiation to functional non hypertrophic chondrocytes remain largely unknown, despite the work on embryologic development and the identification of key growth factors including TGFbeta, Hh, Wnt and FGF. In this study, we asked if we could identify specific biological networks common to the growth factors used (TGFbeta3 or BMP-2). To address this question, we used DNA microarrays and performed large-scale expression profiling of MSC at different time points during their chondrogenic differentiation. By comparing these data with those obtained during the differentiation of MSC into osteoblasts and adipocytes, we identified 318 genes specific for chondrogenesis and developed a new algorithm to classify the genes according to their kinetic profile. We distributed the selected genes in five classes according to their kinetic of expression. We could reconstruct three phases characterized by functional pathways. The first phase corresponds to cell attachment and apoptosis induction; the second phase is characterized by a proliferation/differentiation step, and the third phase is characterized by a differentiation/hypertrophy pathway. Indeed, these data propose new pathways to understand the complexity of MSC differentiation to chondrocytes.
authors.affiliation: Inserm, Montpellier, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mrugala
authors.forename: Nadège
authors.initials: N
authors.lastname: Dossat
authors.forename: Jochen
authors.initials: J
authors.lastname: Ringe
authors.forename: Bruno
authors.initials: B
authors.lastname: Delorme
authors.forename: Amandine
authors.initials: A
authors.lastname: Coffy
authors.forename: Claire
authors.initials: C
authors.lastname: Bony
authors.forename: Pierre
authors.initials: P
authors.lastname: Charbord
authors.forename: Thomas
authors.initials: T
authors.lastname: Häupl
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Daures
authors.forename: Danièle
authors.initials: D
authors.lastname: Noël
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000494:pharmacology; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology; D020219:Chondrogenesis / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering; D053782:Transforming Growth Factor beta3 / Q000378:metabolism / Q000494:pharmacology
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D053782:Transforming Growth Factor beta3