Comparative effects of retinoic acid and jervine on chondrocyte differentiation

Jervine and retinoic acid are both teratogenic to structures which are initially modelled in cartilage. Differences in periods of maximal sensitivity, as well as in certain aspects of the morphological manifestations of exposure, indicate that these two teratogens act via different molecular mechanisms. Here we compare the effects of jervine and retinoic acid in three culture systems which represent sequential stages of the chondrocyte lineage. Proliferation of pluripotent C3H 10T 1/2 cells was decreased by exposure to jervine but was not affected by retinoic acid. Differentiation of high-density "spot" cultures of embryonic limb bud mesenchyme were sensitive to both compounds. Mature chondrocytes were resistant to jervine but "dedifferentiated" after 48-hour exposure to retinoic acid. We conclude that jervine compromises rapidly dividing chondrogenic precursors, whereas retinoic acid has little effect prior to the expression of cartilage-specific proteins.