title: Effect of bone resorbing factors on u-PA and its specific receptor in osteosarcoma cell line.
abstract: This study investigated the effect of bone resorbing factors on the pericellular fibrinolytic system of osteosarcoma NY cells. Parathyroid hormone (PTH), prostaglandin E2, (PGE2) or tumor necrosis factor alpha (TNF-alpha) enhanced the secretion of urokinase-type plasminogen activator (u-PA) antigen and suppressed the secretion of plasminogen activator inhibitor-1 (PAI-1) antigen to the conditioned medium. The former two factors also increased u-PA antigen in the cell surface. Transforming growth factor beta (TGF-beta) enhanced u-PA antigen, but its activity was suppressed due to the increased secretion of PAI-1. The binding assay of [125I]DFP-u-PA to NY cells revealed the presence of a single class of binding sites with a Kd of 5.51 nM and Bmax of 0.92 x 10(5) binding sites/cell. PTH or PGE2 increased Bmax 1.4-fold and 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 Kd or u-PAR mRNA level. Thus, pericellular fibrinolytic activity by u-PA/u-PAR and PAI-1 is modulated by bone resorbing factors.
authors.affiliation: Department of Physiology, Kinki University of Medicine, Osakasayama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nonaka
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: W
authors.initials: W
authors.lastname: Shimada
authors.forename: K
authors.initials: K
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Fukao
authors.forename: S
authors.initials: S
authors.lastname: Ueshima
authors.forename: H
authors.initials: H
authors.lastname: Kikuchi
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: O
authors.initials: O
authors.lastname: Matsuo
mesh_terms: D001862:Bone Resorption / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D012516:Osteosarcoma / Q000737:chemistry*; D010281:Parathyroid Hormone / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: C524898:PLAUR protein, human; D010281:Parathyroid Hormone; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014568:Urokinase-Type Plasminogen Activator; D015232:Dinoprostone