Activation of genes for growth factor and cytokine pathways late in chondrogenic differentiation of ATDC5 cells.
The mouse embryonal carcinoma cell line ATDC5 provides an excellent model system for chondrogenesis in vitro. To understand better the molecular mechanisms of endochondral bone formation, we investigated gene expression profiles during the differentiation course of ATDC5 cells, using an in-house microarray harboring full-length-enriched cDNAs. For 28 days following chondrogenic induction, 507 genes were up- or down-regulated at least 1.5-fold. These genes were classified into five clusters based on their expression patterns. Genes for growth factor and cytokine pathways were significantly enriched in the cluster characterized by increases in expression during late stages of chondrocyte differentiation. mRNAs for decorin and osteoglycin, which have been shown to bind to transforming growth factors-beta and bone morphogenetic proteins, respectively, were found in this cluster and were detected in hypertrophic chondrocytes of developing mouse bones by in situ hybridization analysis. Taken together with assigned functions of individual genes in the cluster, interdigitated interaction between a number of intercellular signaling molecules is likely to take place in the late chondrogenic stage for autocrine and paracrine regulation among chondrocytes, as well as for chemoattraction and stimulation of progenitor cells of other lineages.
Osawa
Aki
A
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan. aki8152@v001.vaio.ne.jp
Kato
Masaki
M
Matsumoto
Eriko
E
Iwase
Katsuro
K
Sugimoto
Takashi
T
Matsui
Tsutomu
T
Ishikura
Hiroshi
H
Sugano
Sumio
S
Kurosawa
Hisashi
H
Takiguchi
Masaki
M
Seki
Naohiko
N
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics*; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D058575:Decorin; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C512906:Ogn protein, mouse; D011509:Proteoglycans