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  • Title: Cortisol downregulates osteoblast alpha 1 (I) procollagen mRNA by transcriptional and posttranscriptional mechanisms.
    Author: Delany AM, Gabbitas BY, Canalis E.
    Journal: J Cell Biochem; 1995 Mar; 57(3):488-94. PubMed ID: 7768983.
    Abstract:
    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.
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