Retinoic acid-induced cartilage resorption: induction of specific changes in protein synthesis and inhibition by tunicamycin.
The addition of retinoic acid to fetal rat bones in culture induces the release of proteoglycans followed by cartilage resorption. In this system retinoic acid markedly suppressed 3H-leucine and 3H-mannose incorporation into acid-precipitable macromolecules, and specifically changed the 3H-leucine incorporation pattern as revealed by gel electrophoresis. Tunicamycin, which selectively inhibits glycosylation of the asparagine residues in proteins, prevented the cartilage cell degradation in response to retinoic acid. Inhibitors of DNA synthesis did not affect the retinoic acid-induced changes indicating that cell division was not required for the cartilage degradation processes induced by retinoic acid. In consideration of our previous and present demonstrations that retinoic acid-induced cartilage resorption required RNA, protein, and glycoprotein synthesis and specifically changed the protein synthesis pattern, we suggest that retinoic acid may exert its action by altering gene expression.