Antiproliferative effect of the C-terminal fragments of parathyroid hormone-related protein, PTHrP-(107-111) and (107-139), on osteoblastic osteosarcoma cells.

Abstract:

:The C-terminal region of parathyroid hormone-related protein (PTHrP) containing the sequence (107-111) appears to be a potent inhibitor of osteoclastic bone resorption. In the present study, we have investigated the effect of human (h)PTHrP (107-139) and hPTHrP (107-111)NH2 on the proliferation of osteoblastic rat osteosarcoma UMR 106 cells. We found that both C-terminal PTHrP peptides, like hPTHrP (1-141), were antimitogenic for these cells, between 1 pM and 10 nM. [Tyr34]hPTHrP (1-34)NH2 was as potent as these peptides but less effective as growth inhibitor in these cells. UMR 106 cells were found to produce and secrete immunoreactive PTHrP. Addition of anti-PTHrP neutralizing antibodies to C- and N-terminal epitopes of PTHrP increased the growth of these cells. Our data suggest that the antiproliferative effect of these C-terminal PTHrP analogs may be independent of cyclic adenosine 3':5'-monophosphate (cAMP) and mediated by protein kinase C. These findings support an autocrine role of PTHrP in bone metabolism.

journal_name

J Cell Physiol

authors

Valín A,García-Ocaña A,De Miguel F,Sarasa JL,Esbrit P

doi

10.1002/(SICI)1097-4652(199702)170:2<209::AID-JCP1

subject

Has Abstract

pub_date

1997-02-01 00:00:00

pages

209-15

issue

2

eissn

0021-9541

issn

1097-4652

pii

10.1002/(SICI)1097-4652(199702)170:2<209::AID-JCP1

journal_volume

170

pub_type

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