Temporal transcriptome of mouse ATDC5 chondroprogenitors differentiating under hypoxic conditions.
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.
Laboratory for Stem Cell Research, Department of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, DK-9220 Aalborg, Denmark.
Li
L
Chen
Trine
T
Fink
Peter
P
Ebbesen
Vladimir
V
Zachar
D053674:Aggrecans; D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D020219:Chondrogenesis / Q000502:physiology*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006025:Glycosaminoglycans / Q000378:metabolism; D000860:Hypoxia; D007328:Insulin / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014158:Transcription, Genetic
C508320:Acan protein, mouse; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D007328:Insulin; D037181:Lectins, C-Type; D010100:Oxygen