Bone and Joint Institute
Microarray analyses of gene expression during chondrocyte differentiation identifies novel regulators of hypertrophy
Document Type
Article
Publication Date
11-1-2005
Journal
Molecular Biology of the Cell
First Page
5316
Last Page
5333
URL with Digital Object Identifier
10.1091/mbc.E05-01-0084
Abstract
Ordered chondrocyte differentiation and maturation is required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear. We used Affymetrix microarrays to examine temporal gene expression patterns during chondrogenic differentiation in a mouse micromass culture system. Robust normalization of the data identified 3300 differentially expressed probe sets, which corresponds to 1772, 481, and 249 probe sets exhibiting minimum 2-, 5-, and 10-fold changes over the time period, respectively. GeneOntology annotations for molecular function show changes in the expression of molecules involved in transcriptional regulation and signal transduction among others. The expression of identified markers was confirmed by RT-PCR, and cluster analysis revealed groups of coexpressed transcripts. One gene that was up-regulated at later stages of chondrocyte differentiation was Rgs2. Overexpression of Rgs2 in the chondrogenic cell line ATDC5 resulted in accelerated hypertrophic differentiation, thus providing functional validation of microarray data. Collectively, these analyses provide novel information on the temporal expression of molecules regulating endochondral bone development. © 2005 by The American Society for Cell Biology.
Notes
This article is freely available from the journal