RGD Reference Report - Basic fibroblast growth factor stimulates collagenase-3 promoter activity in osteoblasts through an activator protein-1-binding site. - Rat Genome Database

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Basic fibroblast growth factor stimulates collagenase-3 promoter activity in osteoblasts through an activator protein-1-binding site.

Authors: Varghese, S  Rydziel, S  Canalis, E 
Citation: Varghese S, etal., Endocrinology. 2000 Jun;141(6):2185-91.
RGD ID: 1626699
Pubmed: PMID:10830307   (View Abstract at PubMed)
DOI: DOI:10.1210/endo.141.6.7504   (Journal Full-text)

Basic fibroblast growth factor (bFGF) stimulates collagenase-3 synthesis in fetal rat osteoblast-enriched (Ob) cells. In this study we examined the mechanism of collagenase-3 regulation in Ob cells. bFGF at 0.6 nM or more increased the transcriptional rate of collagenase-3 by 3- to 7-fold. bFGF at 0.6 nM increased the activity of collagenase-3 promoter-luciferase reporter deletion constructs from -721 to -53 nucleotides transiently transfected into Ob cells by 3- to 5-fold. The minimal bFGF response was retained within the -53 to +28 sequence. Mutational analysis revealed that the bFGF effect was mediated through an activator protein-1 (AP-1)-binding site located at -48 to -42 nucleotides in the promoter. bFGF stimulated the binding of nuclear factors to the collagenase AP-1 site by 3- to 4-fold, as determined by electrophoretic mobility shift assays. Supershift analysis of nuclear extracts revealed that bFGF stimulates the occupancy of AP-1 site by c-Jun, JunB, JunD, c-Fos, FosB, and Fra2. In conclusion, bFGF increases collagenase-3 gene transcription, an effect mediated through an AP-1 site, due to the induction or activation of Jun and Fos family transcription factors. The stimulation of collagenase-3 synthesis by bFGF may be critical in mediating the actions of this growth factor in bone remodeling.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Objects Annotated

Genes (Rattus norvegicus)
Fos  (Fos proto-oncogene, AP-1 transcription factor subunit)
Fosb  (FosB proto-oncogene, AP-1 transcription factor subunit)
Fosl2  (FOS like 2, AP-1 transcription factor subunit)
Jun  (Jun proto-oncogene, AP-1 transcription factor subunit)
Junb  (JunB proto-oncogene, AP-1 transcription factor subunit)
Jund  (JunD proto-oncogene, AP-1 transcription factor subunit)


Additional Information