EFFECT OF BONE-RESORBING FACTORS ON U-PA AND ITS SPECIFIC RECEPTOR INOSTEOSARCOMA CELL-LINE

This study investigated the effect of bone resorbing factors on the pe ricellular fibrinolytic system of osteosarcoma NY cells. Parathyroid h ormone (PTH), prostaglandin E(2), (PGE(2)) or tumor necrosis factor al pha (TNF-alpha) enhanced the secretion of urokinase-type plasminogen a ctivator (u-PA) antigen and suppressed the secretion of plasminogen ac tivator inhibitor-1 (PAI-1) antigen to the conditioned medium. The for mer two factors also increased u-PA antigen in the cell surface. Trans forming growth factor beta (TGF-beta) enhanced u-PA antigen, but its a ctivity was suppressed due to the increased secretion of PAI-1. The bi nding assay of [I-125]DFP-u-PA to NY cells revealed the presence of a single class of binding sites with a K-d of 5.51 nM and B-max of 0.92 x 10(5) binding sites/cell. PTH or PGE(2) increa sed B-max 1.4-fold an d enhanced the u-PA receptor (u-PAR) mRNA level 1.4-fold or 2.4-fold, respectively. However, TGF-beta did not alter either the K-d or u-PAR mRNA level. Thus, pericellular fibrinolytic activity by u-PA/u-PAR and PAI-1 is modulated by bone resorbing factors.