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.