CORTISOL INCREASES INTERSTITIAL COLLAGENASE EXPRESSION IN OSTEOBLASTS BY POSTTRANSCRIPTIONAL MECHANISMS

Glucocorticoids regulate both bone formation and bone resorption, In osteoblasts, they inhibit type I collagen synthesis; however, there is limited information about their effects on interstitial collagenase, the enzyme that degrades type I collagen, We used primary cultures of osteoblast-enriched cells from fetal rat calvariae (Ob cells) to study the effects of cortisol on collagenase expression, Northern blot analysis showed that cortisol increased collagenase transcript levels in a dose and time-dependent manner, which was paralleled by an increase in immunoreactive metalloproteinase in the culture medium, Cortisol increased the half-life of collagenase mRNA from 6 to 12 h in transcription-arrested Ob cells, In contrast, cortisol modestly decreased collagenase gene transcription after 24 h of treatment, The up-regulation of collagenase by cortisol is osteoblast-specific, since the glucocorticoid decreased phorbol la-myristate 13-acetate induced collagenase mRNA expression in rat fibroblasts, a result that agrees with other studies of collagenase gene regulation in fibroblastic cells, In conclusion, cortisol increases interstitial collagenase transcript levels by post-transcriptional mechanisms in osteoblastic cells, Our data demonstrate that glucocorticoids regulate collagenase gene expression in a novel tissue-specific manner, further highlighting the differences in gene regulation between osteoblastic and fibroblastic cells.