ANTIPROLIFERATIVE EFFECT OF THE C-TERMINAL FRAGMENTS OF PARATHYROID HORMONE-RELATED PROTEIN, PTHRP-(107-111) AND PTHRP-(107-139), ON OSTEOBLASTIC OSTEOSARCOMA CELLS

The C-terminal region of parathyroid hormone-related protein (PTHrP) c ontaining the sequence (107-111) appears to be a potent inhibitor of o steoclastic bone resorption. In the present study, we have investigate d the effect of human (h)PTHrP (107-139) and hPTHrP (107-111)NH2 on th e proliferation of osteoblastic rat osteosarcoma UMR 106 cells. We fou nd that both C-terminal PTHrP peptides, like hPTHrP (1-141), were anti mitogenic for these cells, between 1 pM and 10 nM. [Tyr(34)]hPTHrP (1- 34)NH2 was as potent as these peptides but less effective as growth in hibitor in these cells. UMR 106 cells were found to produce and secret e 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-t erminal PTHrP analogs may be independent of cyclic adenosine 3':5'-mon ophosphate (cAMP) and mediated by protein kinase C. These findings sup port an autocrine role of PTHrP in bone metabolism. (C) 1997 Wiley-Lis s, Inc.