Insulin-like growth factor I inhibits the transcription of collagenase 3 in osteoblast cultures.
Insulin-like growth factor (IGF) I is an autocrine regulator of bone remodeling which inhibits bone collagen degradation and interstitial collagenase 3 mRNA levels. The mechanism of this inhibitory effect on collagenase 3 expression is not known. We tested the effects of IGF I on collagenase 3 gene expression in cultures of osteoblast-enriched cells from 22 day fetal rat calvariae (Ob cells) to determine whether transcriptional or posttranscriptional mechanisms were involved in the regulation of the collagenase 3 gene. IGF I at 10-100 nM caused a dose-dependent decrease in collagenase mRNA and protein levels. IGF I did not modify the half-life of collagenase 3 mRNA in transcriptionally arrested Ob cells, whereas it decreased the levels of interstitial collagenase 3 heterogeneous nuclear RNA. In addition, IGF I decreased the rates of transcription of the collagenase gene and the activity of a 2.1 kilobase collagenase 3 promoter construct transiently transfected into Ob cells. In conclusion, IGF I decreases the expression of collagenase 3 mRNA by transcriptional mechanisms.
Rydziel
S
S
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Delany
A M
AM
Canalis
E
E
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics*; D004622:Embryo, Mammalian; D015870:Gene Expression; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13; D010006:Osteoblasts / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D014158:Transcription, Genetic; D014162:Transfection
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D012194:RNA-Directed DNA Polymerase; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat