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 o f YM9429 on chondrogenic differentiation was investigated using mouse embryonic carcinoma ATDC5 cells that produce chondrocyte specific extr acellular matrix upon insulin stimulation. YM9429 at concentrations th at showed no growth-inhibitory effect on logarithmic proliferating cel ls suppressed insulin-mediated increases in Alcian blue staining and e xpression of type II collagen almost completely. Under the identical c onditions, insulin-stimulated cell growth was only partially blocked b y 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 proce ss. These results indicate that YM9429 selectively inhibits in vitro c hondrogenic differentiation of ATDC5 cells. (C) 1996 Academic Press, I nc.