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Status |
Public on Jan 30, 2008 |
Title |
Multipotent mesenchymal stromal cells: identification of pathways common to TGFβ3/BMP2-induced chondrogenesis |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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 TGFβ, Hh, Wnt and FGF families. In this study, we asked if we could identify specific biological networks independently from the growth factor used (TGFβ-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 α5 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. Keywords: dose response
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Overall design |
To identify genes involved in TGFβ3/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 TGFβ3, gene expression was determined by microarray hybridization after 1, 3, 7 and 21 days and compared to the undifferentiated MSC.
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Contributor(s) |
Mrugala D, Dossat N, Ringe J, Delorme B, Coffy A, Bony C, Charbord P, Häupl T, Daures J, Noël D, Jorgensen C |
Citation(s) |
19196040 |
Submission date |
Jan 29, 2008 |
Last update date |
Mar 25, 2019 |
Contact name |
Thomas Häupl |
E-mail(s) |
thomas.haeupl@charite.de
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Phone |
+49 30 450513293
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Organization name |
Charité
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Department |
Rheumatology
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Street address |
Charitéplatz 1
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City |
Berlin |
ZIP/Postal code |
10117 |
Country |
Germany |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (30)
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GSM260660 |
human BM MSC unstimulated rep 4 |
GSM260661 |
human BM MSC unstimulated rep 5 |
GSM260662 |
human BM MSC unstimulated rep 6 |
GSM260663 |
human BM MSC BMP2 stimulated day 1 rep 1 |
GSM260664 |
human BM MSC BMP2 stimulated day 1 rep 2 |
GSM260665 |
human BM MSC BMP2 stimulated day 1 rep 3 |
GSM260666 |
human BM MSC BMP2 stimulated day 3 rep 1 |
GSM260667 |
human BM MSC BMP2 stimulated day 3 rep 2 |
GSM260668 |
human BM MSC BMP2 stimulated day 3 rep 3 |
GSM260669 |
human BM MSC BMP2 stimulated day 7 rep 1 |
GSM260670 |
human BM MSC BMP2 stimulated day 7 rep 2 |
GSM260671 |
human BM MSC BMP2 stimulated day 7 rep 3 |
GSM260672 |
human BM MSC BMP2 stimulated day 21 rep 1 |
GSM260673 |
human BM MSC BMP2 stimulated day 21 rep 2 |
GSM260674 |
human BM MSC BMP2 stimulated day 21 rep 3 |
GSM260675 |
human BM MSC TGFb3 stimulated day 1 rep 1 |
GSM260676 |
human BM MSC TGFb3 stimulated day 1 rep 2 |
GSM260677 |
human BM MSC TGFb3 stimulated day 1 rep 3 |
GSM260678 |
human BM MSC TGFb3 stimulated day 3 rep 1 |
GSM260679 |
human BM MSC TGFb3 stimulated day 3 rep 2 |
GSM260680 |
human BM MSC TGFb3 stimulated day 3 rep 3 |
GSM260681 |
human BM MSC TGFb3 stimulated day 7 rep 1 |
GSM260682 |
human BM MSC TGFb3 stimulated day 7 rep 2 |
GSM260683 |
human BM MSC TGFb3 stimulated day 7 rep 3 |
GSM260684 |
human BM MSC TGFb3 stimulated day 21 rep 1 |
GSM260685 |
human BM MSC TGFb3 stimulated day 21 rep 2 |
GSM260686 |
human BM MSC TGFb3 stimulated day 21 rep 3 |
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Relations |
BioProject |
PRJNA108545 |
Supplementary file |
Size |
Download |
File type/resource |
GSE10315_RAW.tar |
244.3 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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