Half-life of synovial cell collagenase mRNA is modulated by phorbol myristate acetate but not by all-trans-retinoic acid or dexamethasone.

As part of our studies on the mechanisms controlling the synthesis of the neutral proteinase collagenase by rabbit synovial cells, we used a cDNA clone to measure total collagenase mRNA levels and to determine mRNA half-life. Phorbol myristate acetate was used to induce collagenase synthesis while all-trans-retinoic acid and dexamethasone were used to inhibit it. Cells stimulated with phorbol myristate acetate contained substantial amounts of collagenase mRNA, but cells treated with all-trans-retinoic acid or dexamethasone contained decreased amounts of collagenase mRNA which correlated well with levels of collagenase protein. Studies on mRNA half-life showed that the t1/2 for total poly(A+) RNA was about 25 h, while that of collagenase varied from as short as 12 h to as long as 36 h. The half-life was not affected by treatment with all-trans-retinoic acid or dexamethasone but was affected by the level of induction of collagenase mRNA: the greater the amount of collagenase mRNA induced, the longer the t1/2. We conclude that our data are consistent with the hypothesis that retinoic acid and dexamethasone act at the level of transcription to decrease collagenase production and the increased level of collagenase mRNA resulting from stimulation with phorbol esters is, in part, due to increased stability of the induced collagenase mRNA.