Antiproliferative effect of the C-terminal fragments of parathyroid hormone-related protein,PTHrP-(107–111) and (107–139), on osteoblastic osteosarcoma cells |
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Authors: | Alvaro Valí n,Adolfo Garcí a-Ocañ a,Fernando De Miguel,José L. Sarasa,Pedro Esbrit |
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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. J. Cell. Physiol. 170:209–215, 1997. © 1997 Wiley-Liss, Inc. |
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