Independence of cell shape and loss of cartilage matrix production during retinoic acid treatment of cultured chondrocytes.

Retinoic acid has been shown to cause chondrocytes in culture to flatten and to inhibit the synthesis of cartilage specific components. Since the biochemical expression of chondrocytes is considered to be dependent on cell shape, it has been proposed that retinoic acid acts on these cells primarily by causing a change in cell morphology. This hypothesis was tested by culturing chick sternal chondrocytes suspended in methyl cellulose, which prevents cell flattening. Cultures were labeled with [35S]methionine and differentiation was assessed by polyacrylamide gel electrophoresis. The results showed that retinoic acid-treated chondrocytes in suspension remained rounded but synthesized proteins characteristic of flattened or dedifferentiated chondrocytes. Chondrocytes exposed to retinoic acid in suspension became fibroblastic when placed in monolayer culture in the absence of retinoic acid. This effect was irreversible after 2 weeks of culture. These results suggest that retinoic acid has a direct molecular or biochemical effect on the chondrocyte and that the cell shape change is secondary.