Cortisol increases interstitial collagenase expression in osteoblasts by post-transcriptional 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 12-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.
Delany
A M
AM
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Jeffrey
J J
JJ
Rydziel
S
S
Canalis
E
E
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis*; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis; D020781:Matrix Metalloproteinase 1; D009928:Organ Specificity; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D012886:Skull; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D012333:RNA, Messenger; D011994:Recombinant Proteins; D008156:Luciferases; D017364:Collagenases; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone