Interaction of AP-1 and the ctgf gene: a possible driver of chondrocyte hypertrophy in growth cartilage

• Published in: Journal of bone and mineral metabolism Vol. 21; no. 4; pp. 205 - 210
• Main Authors: MORITAN, Norifumi H, KUBOTA, Satoshi, EGUCHI, Takanori, FUKUNAGA, Tomohiro, YAMASHIRO, Takashi, TAKANO-YAMAMOTO, Teruko, TAHARA, Hideki, OHYAMA, Kazumi, SUGAHARA, Toshio, TAKIGAWA, Masaharu
• Format: Journal Article
• Language: English
• Published: Tokyo Springer 01-01-2003; Springer Nature B.V
• Subjects: Binding Sites; Biological and medical sciences; Cartilage - growth & development; Cartilage - pathology; Cell Division - genetics; Cells, Cultured; Chondrocytes - pathology; Connective Tissue Growth Factor; Enhancer Elements, Genetic; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Genes, fos - genetics; Growth Plate - cytology; Growth Plate - metabolism; Humans; Hypertrophy - genetics; Hypertrophy - pathology; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Proto-Oncogenes - genetics; Skeleton and joints; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Vertebrates: osteoarticular system, musculoskeletal system; Human; Immunohistochemistry; Cell culture; Chondrocyte; Growth; Exploration; Cell differentiation; Experimental study; Gene expression; In vitro; Osteoarticular system; Pathology; Regulation(control); Histopathology; Epiphyseal cartilage; Growth factor; Hypertrophy; Transcription factor AP1
• ISSN: 0914-8779; 1435-5604
• DOI: 10.1007/s00774-003-0410-1

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.