Interaction of AP-1 and the ctgf gene: a possible driver of chondrocyte hypertrophy in growth cartilage.
The expression of the connective tissue growth factor ( ctgf) gene increases along with the differentiation of growth cartilage cells, and the highest expression is observed in the hypertrophic stage. Similarly, recent reports demonstrated c- fos expression in chondrocytes in the early hypertrophic zone of growth cartilage, and suggested that the c- fos gene may play a crucial role in the regulation of hypertrophic differentiation. A chondrocytic human cell line, HCS-2/8, is known to retain a variety of chondrocytic phenotypes. When such cells were kept overconfluent, they expressed increasing levels of c- fos transcripts along a time course phenotypically similar to that of hypertrophic differentiation. Moreover, by using a competitive electromobility-shift assay, we found that AP-1, a Fos/Jun heterodimer, in HCS-2/8 was capable of binding not only to a typical AP-1-binding DNA fragment but also to the enhancer fragment of the ctgf gene. Based on the findings above, we hypothesize that, prior to hypertrophic differentiation, AP-1-related oncogenes are activated and that their gene products subsequently activate ctgf gene expression, which might eventually induce hypertrophy.
Moritani
Norifumi H
NH
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
Kubota
Satoshi
S
Eguchi
Takanori
T
Fukunaga
Tomohiro
T
Yamashiro
Takashi
T
Takano-Yamamoto
Teruko
T
Tahara
Hideki
H
Ohyama
Kazumi
K
Sugahara
Toshio
T
Takigawa
Masaharu
M
D001665:Binding Sites; D002356:Cartilage / Q000254:growth & development* / Q000473:pathology*; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D019902:Chondrocytes / Q000473:pathology*; D055513:Connective Tissue Growth Factor; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000235:genetics; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy / Q000235:genetics / Q000473:pathology; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D011519:Proto-Oncogenes / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D018808:Transcription Factor AP-1; D055513:Connective Tissue Growth Factor