Inhibition of insulin-induced chondrogenic differentiation of embryonic carcinoma cells by a teratogenic compound YM9429.

A teratogenic compound cis-1-[4-(p-menthane 8-yloxy)phenyl]piperidine (YM9429) induces cleft palate selectively in rat fetuses. The effect of YM9429 on chondrogenic differentiation was investigated using mouse embryonic carcinoma ATDC5 cells that produce chondrocyte specific extracellular matrix upon insulin stimulation. YM9429 at concentrations that showed no growth-inhibitory effect on logarithmic proliferating cells suppressed insulin-mediated increases in Alcian blue staining and expression of type II collagen almost completely. Under the identical conditions, insulin-stimulated cell growth was only partially blocked by the compound. The early response genes such as c-fos and c-jun were induced by insulin even in the presence of YM9429. On the other hand, YM9429 inhibited accumulation of cAMP during the differentiation process. These results indicate that YM9429 selectively inhibits in vitro chondrogenic differentiation of ATDC5 cells.