Effect of elastase in reversing the de-differentiation of rabbit costal chondrocytes in culture induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA)

Abstract

As elastase is known to affect cell functions in various cell systems, its effects on the functions of control and 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated chondrocytes in vitro were examined. Pretreatment of chondrocytes with TPA (10(-8) M) for 48 h significantly enhanced DNA synthesis, inhibited glycosaminoglycan (GAG) synthesis and inhibited the increase in ornithine decarboxylase (ODC) activity in response to parathyroid hormone (PTH) relative to values in control cultures. Addition of elastase (1, 10 and 50 ng/ml) for 24 h partially inhibited the de-differentiated phenotypes induced by TPA such as the decreased synthesis of GAG and decreased response of ODC activity to PTH without affecting the DNA synthesis. Moreover, elastase significantly increased both the basal level of cyclic AMP and that on PTH treatment of TPA-pretreated cells. These results suggested that elastase partially restored the differentiated phenotypes of de-differentiated chondrocytes probably through its effect in increasing the level of intracellular cyclic AMP.