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Insulin-like growth factor I inhibits the transcription of collagenase 3 in osteoblast cultures

โœ Scribed by Sheila Rydziel; Anne M. Delany; Ernesto Canalis


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
188 KB
Volume
67
Category
Article
ISSN
0730-2312

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โœฆ Synopsis


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.


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