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Cortisol downregulates osteoblast α1(I) procollagen mRNA by transcriptional and posttranscriptional mechanisms
Author(s) -
Delany Anne M.,
Gabbitas Bari Y.,
Canalis Ernesto
Publication year - 1995
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/jcb.240570314
Subject(s) - procollagen peptidase , osteoblast , cycloheximide , glucocorticoid , medicine , endocrinology , transcription (linguistics) , gene expression , calvaria , messenger rna , biology , gene , chemistry , microbiology and biotechnology , protein biosynthesis , biochemistry , in vitro , linguistics , philosophy
Glucocorticoids decrease osteoblast proliferation and type I collagen production, and this may play a role in the development of glucocorticoid‐induced osteoporosis. Osteoblast‐enriched cultures derived from fetal rat calvaria were used to determine the mechanisms by which cortisol decreases α1(I) procollagen expression in bone cells. A 24 h treatment with cortisol decreased collagen synthesis in these cultures in a dose‐dependent manner. Cortisol decreased α1(I) procollagen transcripts in a dose‐ and time‐dependent manner as well. Repression of α1(I) procollagen transcripts was evident as early as 2 h of treatment and was maximal after 48 h of treatment. Nuclear run‐off assays showed that cortisol downregulated transcription of the α1(I) procollagen gene. In addition, pretreatment with cortisol decreased the stability of α1(I) procollagen mRNA in transcription‐arrested osteoblast cultures. The ability of cortisol to downregulate α1(I) procollagen transcripts was sensitive to cycloheximide treatment, suggesting that the gene is under “secondary control” by glucocorticoids. Since cortisol decreases α1(I) procollagen gene transcription in osteoblasts but does not affect α1(I) procollagen gene transcription in fibroblasts, we suggest that the mechanisms controlling glucocorticoid repression of collagen expression are cell‐type specific.