Increased level of translatable collagenase messenger ribonucleic acid in rabbit synovial fibroblasts treated with phorbol myristate acetate or crystals of monosodium urate monohydrate

Abstract

We studied mechanisms governing production of the neutral proteinase collagenase by synovial cells. We used a model system of monolayer cultures of rabbit synovial fibroblasts stimulated to produce collagenase by treatment with phorbol myristate acetate or crystals of monosodium urate monohydrate. mRNAs from these and untreated cells were translated in a wheat germ cell-free system. Collagenase was not present in the culture medium or in the in vitro translation products of mRNA from untreated cells but was present in both the medium and translation products of stimulated cells, as analyzed by gel electrophoresis and immunoprecipitation with monospecific antibody. Induction of collagenase was prevented by treatment of the cells with alpha-amanitin (2 mug/ mL), an inhibitor of mRNA synthesis. We have concluded that the induction of collagenase synthesis by either phorbol myristate acetate or urate crystals is due to an increased level of translatable mRNA.