Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MiRNA expression microrarray of MSC grown on bone inducing scaffolds

ABSTRACT: Mesenchymal Stem Cells have been seeded on calcium based biomaterials. miRNA expression is evaluated at day 0 (unseeded cells), day 5, and day 10, in order to study miRNA differential expressions at different time points and infer if biomaterial induced miRNA expression variation able to differentiate stem cells towards the osteoblasts lineage.

ORGANISM(S): Homo Sapiens

SUBMITTER: Federica Viti

PROVIDER: E-MTAB-3441 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Human mesenchymal stem 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 and non hypertrophic chondrocytes remain largely unknown, despite the work on embryologic development and the identification of key growth factors including members of the TGFbeta, Hh, Wnt and FGF families. In this study, we asked if we could identify specific biological networks independently from the growth factor used (TGFbeta-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 chondral differentiation. By comparing these data with those obtained during their differentiation into osteoblasts and adipocytes, we identified 318 genes specific for chondrogenesis. We distributed the selected genes in 5 classes according to their kinetic of expression and used the Ingenuity software in order to identify new biological networks. We could reconstruct 3 phases for chondral differentiation, characterized by functional pathways. The first phase corresponds to cell attachment and apoptosis prevention with the up-regulation of √é¬±5 integrins, BCL6, NFIL3, RGS2 and down-regulation of CTGF and CYR61. The second phase is characterized by a proliferation/differentiation step with the continuous expression of MAF, PGF, HGMA1 or NOTCH3, CHI3L1, WNT5A, LEPR. Finally, the last step of differentiation/hypertrophy is characterized by expression of DKK1, APOD/E, SERPINF1 and TIMP4. These data propose new pathways to understand the complexity of MSC differentiation to chondrocytes and new potential targets for cell therapy applied to cartilage repair. Experiment Overall Design: To identify genes involved in TGFbeta03/BMP2-induced chondrogenesis, MSC were isolated from human bone marrow aspirates by adherence to culture dishes and cultivated to passage 3. After induction of chondrogenic differentiation with BMP2 or TGFbeta-3, gene expression was determined by microarray hybridization after 1, 3, 7 and 21 days and compared to the undifferentiated MSC.

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MiRNA expression microrarray of MSC grown on bone inducing scaffolds

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