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Status |
Public on Nov 14, 2012 |
Title |
Involvement of ERK, Wnt and BMP2 signaling in human articular chondrocyte dedifferentiation in monolayer culture |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Objective: When primary chondrocytes are cultured in monolayer, they undergo dedifferentiation during which they lose their phenotype and their capacity to form cartilage. Dedifferentiation is an obstacle for cell therapy for cartilage degeneration. In this study, we aimed to systemically evaluate the changes in gene expression during dedifferentiation of human articular chondrocytes to identify underlying mechanisms. Methods: RNA was isolated from monolayer-cultured primary human articular chondrocytes at serial passages. Gene expression was analyzed by microarray. Based on the microarray analysis, relevant genes and pathways were identified. Their functions in chondrocyte dedifferentiation were further investigated in detail. Results: In vitro expanded human chondrocytes showed progressive changes in gene expression during dedifferentiation. Strikingly, an overall decrease in total gene expression was detected. Genes in the Wnt and BMP pathways exhibited significant changes in expression. The non-canonical rather than the canonical Wnt pathway was found to be involved in the loss of collagen II synthesis. BMP2 was able to decelerate the dedifferentiation and reinforce the maintenance of chondrocyte phenotype in monolayer culture. DNA methylation was in part responsible for the expression downregulation of a set of genes. Conclusion: Our study revealed the roles of ERK, Wnt and BMP pathways as well as DNA methylation in chondrocyte dedifferentiation in monolayer culture.
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Overall design |
RNA human chondrocytes were allowed to dedifferentiate for 8 passages. RNA was isolated at week 0, 2 ,4, 6 and 8, which was subjected to whole genome gene expression analysis.
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Contributor(s) |
Ma B, Leijten JC, Wu L, Post J, Karperien M |
Citation(s) |
23376013 |
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Submission date |
Nov 13, 2012 |
Last update date |
Aug 16, 2018 |
Contact name |
Jeroen Leijten |
Organization name |
University of Twente
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Street address |
Drienerlolaan 5
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City |
Enschede |
ZIP/Postal code |
7522NB |
Country |
Netherlands |
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Platforms (1) |
GPL6947 |
Illumina HumanHT-12 V3.0 expression beadchip |
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Samples (20)
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Relations |
BioProject |
PRJNA179378 |
Supplementary file |
Size |
Download |
File type/resource |
GSE42235_RAW.tar |
6.2 Mb |
(http)(custom) |
TAR |
GSE42235_non-normalized.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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