Gene Expression Profile of Multipotent Mesenchymal Stromal Cells: Identification of Pathways Common to TGFβ3/BMP2-Induced Chondrogenesis
Gene Expression Profile of Multipotent Mesenchymal Stromal Cells: Identification of Pathways Common to TGFβ3/BMP2-Induced Chondrogenesis
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DOI：
10.1089/clo.2008.0070
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发表时间：
2009-03-01
期刊：
影响因子：
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通讯作者：
Jorgensen, Christian
中科院分区：
文献类型：
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作者：
Mrugala, Dominique;Dossat, Nadege;Jorgensen, Christian
多能间充质基质细胞(MSC)在软骨修复新的治疗策略方面显示出很高的潜力。然而，尽管对胚胎发育和关键生长因子包括转化生长因子β、HH、WNT和成纤维细胞生长因子进行了鉴定，但其向功能性非肥大软骨细胞分化的途径仍很不清楚。在这项研究中，我们询问是否可以确定所使用的生长因子(转化生长因子β3或骨形态发生蛋白-2)共同的特定生物网络。为了解决这个问题，我们使用了DNA微阵列，并在MSC软骨分化的不同时间点进行了大规模的表达谱分析。通过将这些数据与MSC向成骨细胞和脂肪细胞分化过程中获得的数据进行比较，我们确定了318个软骨形成特异性基因，并开发了一种新的算法，根据这些基因的动力学特征对这些基因进行分类。我们根据它们的表达动力学将所选择的基因分为五类。我们可以重建以功能通路为特征的三个阶段。第一阶段为细胞贴壁和诱导细胞凋亡；第二阶段为增殖/分化阶段；第三阶段为分化/肥大途径。事实上，这些数据为理解MSC向软骨细胞分化的复杂性提供了新的途径。
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 TGF beta, Hh, Wnt and FGF. In this study, we asked if we could identify specific biological networks common to the growth factors used (TGF beta 3 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.