REGULATION OF SCU-PA SECRETION AND U-PA RECEPTOR EXPRESSION IN OSTEOBLAST-LIKE CELLS

Citation
T. Nonaka et al., REGULATION OF SCU-PA SECRETION AND U-PA RECEPTOR EXPRESSION IN OSTEOBLAST-LIKE CELLS, Cell structure and function, 18(5), 1993, pp. 355-362
Citations number
43
Categorie Soggetti
Cytology & Histology
Journal title
ISSN journal
03867196
Volume
18
Issue
5
Year of publication
1993
Pages
355 - 362
Database
ISI
SICI code
0386-7196(1993)18:5<355:ROSSAU>2.0.ZU;2-N
Abstract
The production of proteolytic enzymes by osteoblasts is considered imp ortant for initiating osteoclastic bone resorption. Using the establis hed cell line NY as an example of osteoblast-like cells, the effect of intracellular cyclic AMP (cAMP) and protein kinase C (PKC) on plasmin ogen activator secretion and its specific binding to the cells were in vestigated. HT-1080 cells were used as the control. NY cells predomina ntly secrete single-chain urokinase-type plasminogen activator (scu-PA ) and some two-chain u-PA. Both scu-PA and u-PA were present in the ce ll surface and cell lysate of NY cells, and their distribution in HT-1 080 cells was quite similar to that of NY cells. Exposing cells to pho rbol myristate acetate (PMA) or dibutyryl cyclic AMP (db cAMP) enhance d the secretion of scu-PA and two-chain u-PA, whereas 1-(5-isoquinolin ylsulfonyl)-2-methylpiperazine (H7) decreased scu-PA secretion, indica ting that it is enhanced by protein kinase C (PKC) as well as by cAMP in NY cells. On the other hand, in HT-1080 cells, PMA decreased the le vel of two-chain u-PA secretion into the conditioned medium. The bindi ng assay of I-125-DFP-u-PA to NY cells revealed the presence of a sing le class of binding sites with a K-d Of 2.23 nM and B-max of 0.82 x 10 (6) binding sites/cell. PMA however, altered neither the K-d nor the B -max. Dibutyryl cAMP increased the B-max 1.9 fold. Thus, NY cells secr ete u-PA and express specific binding sites on the cell surface, which are modulated by cAMP and PKC. The u-PA/u-PA receptor system may cont ribute to osteoblastic bone resorption.