Gene expression profile of multipotent mesenchymal stromal cells: Identification of pathways common to TGFbeta3/BMP2-induced chondrogenesis

Cloning Stem Cells. 2009 Mar;11(1):61-76. doi: 10.1089/clo.2008.0070.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Protein 2 / pharmacology
  • Chondrocytes / cytology*
  • Chondrocytes / physiology
  • Chondrogenesis / genetics*
  • Chondrogenesis / physiology
  • Gene Expression Profiling*
  • Humans
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Tissue Engineering
  • Transforming Growth Factor beta3 / metabolism
  • Transforming Growth Factor beta3 / pharmacology

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Transforming Growth Factor beta3