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

J Cell Physiol. 1997 Feb;170(2):209-15. doi: 10.1002/(SICI)1097-4652(199702)170:2<209::AID-JCP13>3.0.CO;2-C.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms
  • Cell Division / drug effects*
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Growth Inhibitors / pharmacology*
  • Humans
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Osteosarcoma
  • Parathyroid Hormone / biosynthesis
  • Parathyroid Hormone / pharmacology
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments / pharmacology*
  • Protein Biosynthesis
  • Proteins / pharmacology*
  • Rats
  • Teriparatide / pharmacology
  • Tumor Cells, Cultured


  • Growth Inhibitors
  • PTHLH protein, human
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • Proteins
  • parathyroid hormone-related protein (107-111)
  • Teriparatide
  • parathyroid hormone-related protein (1-141)
  • parathyroid hormone-related protein (107-139)
  • Cyclic AMP-Dependent Protein Kinases