CORTISOL DOWN-REGULATES OSTEOBLAST ALPHA-1(I) PROCOLLAGEN MESSENGER-RNA 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. (C) 1995 Wiley-Liss, Inc.