Cortisol downregulates osteoblast alpha 1 (I) procollagen mRNA by transcriptional and posttranscriptional mechanisms.
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 alpha 1 (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 alpha 1 (I) procollagen transcripts in a dose- and time-dependent manner as well. Repression of alpha 1 (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 alpha 1 (I) procollagen gene. In addition, pretreatment with cortisol decreased the stability of alpha 1 (I) procollagen mRNA in transcription-arrested osteoblast cultures. The ability of cortisol to downregulate alpha 1 (I) procollagen transcripts was sensitive to cycloheximide treatment, suggesting that the gene is under "secondary control" by glucocorticoids. Since cortisol decreases alpha 1 (I) procollagen gene transcription in osteoblasts but does not affect alpha 1 (I) procollagen gene transcription in fibroblasts, we suggest that the mechanisms controlling glucocorticoid repression of collagen expression are cell-type specific.
Delany
A M
AM
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Gabbitas
B Y
BY
Canalis
E
E
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology*; D010006:Osteoblasts / Q000378:metabolism*; D010024:Osteoporosis / Q000139:chemically induced / Q000378:metabolism; D011347:Procollagen / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects*
D011347:Procollagen; D006854:Hydrocortisone