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Insulin‐like growth factor I inhibits the transcription of collagenase 3 in osteoblast cultures
Author(s) -
Rydziel Sheila,
Delany Anne M.,
Canalis Ernesto
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19971101)67:2<176::aid-jcb3>3.0.co;2-u
Subject(s) - collagenase , osteoblast , interstitial collagenase , autocrine signalling , gene expression , messenger rna , biology , transfection , microbiology and biotechnology , growth factor , medicine , endocrinology , cell culture , chemistry , gene , in vitro , enzyme , biochemistry , receptor , genetics
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. J. Cell. Biochem. 67:176–183, 1997. © 1997 Wiley‐Liss, Inc.