Parathyroid hormone-related protein (107-139) decreases alkaline phosphatase in osteoblastic osteosarcoma cells UMR 106 by a protein kinase C-dependent pathway

The C-terminal (107-111) region of parathyroid hormone-related protein (PTHrP) appears to inhibit osteoclastic bone resorption, and to affect osteoblastic growth and differentiation. We tested the effect of human PTHrP (107-139) on alkaline phosphatase (ALP) activity in osteoblastic osteosarcoma UMR 106 cells. We found that this C-terminal PTHrP peptide, between 10 nM and 10 fM, inhibited ALP activity in these cells during the log phase of growth. Human PTHrP (1-34) amide and human PTHrP (1-141) were as potent as PTHrP (107-139) in growing UMR 106 cells. This inhibitory effect of 10 nM PTHrP (107-139) on ALP activity was also observed in serum-depleted cells, and in the presence of 10 nM dexamethasone, which increased ALP activity by 40% in these cells. In addition, this effect of PTHrP (107-139) was blunted by 25 nM bisindolylmaleimide I, a protein kinase C inhibitor. These results support a role for the C-terminal region of PTHrP as a modulator of bone formation.