TY - JOUR
T1 - Temporal Transcriptome of Mouse ATDC5 Chondroprogenitors Differentiating under Hypoxic Conditions
AU - Chen, Li
AU - Fink, Trine
AU - Ebbesen, Peter
AU - Zachar, Vladimir
PY - 2006/6
Y1 - 2006/6
N2 - The formation of cartilage takes place in vivo in an environment of reduced oxygen tension. To study the effect of hypoxia on the process of chondrogenesis, ATDC5 mouse chondroprogenitor cells were induced to differentiate by the addition of insulin and cultured under ambient and hypoxic conditions corresponding to 21% and 1% O2 in the gas phase, respectively. The production of extracellular proteoglycans as well as the transcriptional profile of 104 selected genes was determined by real-time RT-PCR. Hypoxia alone induced early chondrogenesis as evidenced by the synthesis of glycosaminoglycans and expression of aggrecan and collagen type II genes. Surprisingly, however, hypoxic incubation of insulin-treated cells delayed and suppressed the insulin-mediated early chondrogenesis and almost completely blocked hypertrophic differentiation. Analysis of the gene expression yielded several clues as to the mechanisms involved. In addition, a group of genes was identified that have not previously been associated with hypoxia, including Ak4, Akt3, Col X, Fmod, Ier3, IGFbp4, MafF, Mxi1, Rcor2, Rras, Sox6, Tnni2, Wnt5a, and Zfp313.
AB - The formation of cartilage takes place in vivo in an environment of reduced oxygen tension. To study the effect of hypoxia on the process of chondrogenesis, ATDC5 mouse chondroprogenitor cells were induced to differentiate by the addition of insulin and cultured under ambient and hypoxic conditions corresponding to 21% and 1% O2 in the gas phase, respectively. The production of extracellular proteoglycans as well as the transcriptional profile of 104 selected genes was determined by real-time RT-PCR. Hypoxia alone induced early chondrogenesis as evidenced by the synthesis of glycosaminoglycans and expression of aggrecan and collagen type II genes. Surprisingly, however, hypoxic incubation of insulin-treated cells delayed and suppressed the insulin-mediated early chondrogenesis and almost completely blocked hypertrophic differentiation. Analysis of the gene expression yielded several clues as to the mechanisms involved. In addition, a group of genes was identified that have not previously been associated with hypoxia, including Ak4, Akt3, Col X, Fmod, Ier3, IGFbp4, MafF, Mxi1, Rcor2, Rras, Sox6, Tnni2, Wnt5a, and Zfp313.
KW - Aggrecans
KW - Animals
KW - Anoxia
KW - Cartilage
KW - Cell Differentiation
KW - Cell Line
KW - Chondrogenesis
KW - Collagen Type II
KW - Extracellular Matrix Proteins
KW - Gene Expression
KW - Gene Expression Profiling
KW - Glycosaminoglycans
KW - Insulin
KW - Lectins, C-Type
KW - Mice
KW - Molecular Sequence Data
KW - Oligonucleotide Array Sequence Analysis
KW - Oxygen
KW - Proteochondroitin Sulfates
KW - Stem Cells
KW - Transcription, Genetic
U2 - 10.1016/j.yexcr.2006.02.013
DO - 10.1016/j.yexcr.2006.02.013
M3 - Journal article
C2 - 16580664
SN - 0014-4827
VL - 312
SP - 1727
EP - 1744
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 10
ER -