Calcium ionophore and phorbol myristate acetate synergistically inhibited proteoglycan biosynthesis in articular chondrocytes by prostaglandin independent mechanism

In rabbit articular chondrocytes, phorbol myristate acetate (PMA), 1,2-dioctanoyl-sn-glycerol (DG) and calcium ionophore (A23187), reduced the proteoglycan synthesis, in a dose-dependent manner. The combined treatment by PMA and A23187 resulted in an enhanced inhibition of proteoglycan production, indicating a synergistic effect. In presence of PMA or A23187, the release of prostaglandin E 2 (PGE 2 ) was dramatically increased. The addition of indomethacin and BW755c to chondrocytes stimulated by PMA or A23187, suppressed the liberation of PGE 2 , but did not stop the decrease of proteoglycan synthesis.