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Transforming growth factor‐beta and fibroblast growth factor act synergistically to inhibit collagen II synthesis through a mechanism involving regulatory DNA sequences
Author(s) -
Horton Walter E.,
Higginbotham Jill D.,
Chandrasekhar Srinivasan
Publication year - 1989
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041410103
Subject(s) - growth factor , fibroblast growth factor , chondrocyte , transforming growth factor , enhancer , dna synthesis , type ii collagen , microbiology and biotechnology , transforming growth factor beta , biology , epidermal growth factor , fibroblast growth factor receptor 3 , chemistry , procollagen peptidase , transcription factor , cartilage , gene , cell culture , dna , biochemistry , anatomy , receptor , genetics
Abstract Transforming growth factor‐beta (TGF‐β) and fibroblast growth factor (FGF) are two growth factors that will modulate chondrocyte growth and matrix synthesis. Here we report that these two growth factors act in a synergistic fashion to suppress the synthesis of type II collagen by embryonic chicken sternal chondrocytes. Treatment of chondrocytes with 20 ng/ml TGF‐β or 100 ng/ml FGF (acidic or basic) results in a 60–70% suppression of expression of the pro α1 chain of type II collagen. By comparison, when chondrocytes are exposed to a combination of 1 ng/ml TGF‐β and 10 ng/ml FGF, a complete suppression of type II collagen synthesis was observed. Epidermal growth factor (EGF), platelet‐derived growth factor (PDGF), or insulin‐like growth factor‐1 (IGF‐1) produce no suppression of synthesis either individually or in combination with TGF‐β. The decreased expression of the protein results from a decrease in the steady‐state level of the mRNA transcript coding for type II procollagen, as indicated by a northern analysis. Finally, chondrocytes transfected with a plasmid carrying the CAT gene driven by the collagen II promoter/enhancer sequence displayed high levels of CAT activity when cultured in control media, but treatment of the cells with a combination of the two growth factors resulted in a dramatic reduction of CAT activity, indicating diminished promoter activity. These results suggest that both TGF‐β and FGF can down‐regulate transcription of the collagen II gene through regulatory DNA sequences in the promoter and/or enhancer region. In addition, the finding of synergy suggests that these two growth factors may act through different pathways.