Comparison of the Effects of Synthetic Human Parathyroid Hormone (PTH)-(l–34)-Related Peptide of Malignancy and Bovine PTH-(l–34) on Bone Formation and Resorption in Organ Culture*

Abstract

We have compared the effects of synthetic amino-terminal human PTH-(1-34)-related peptide (PTHrP) of malignancy with those of synthetic bovine PTH-(1-34) in cultures of half-calvariae from 21-day-old fetal rats and of parietal bones from 7-day neonatal mice. Incorporation of [3H] proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP), and percent collagen synthesis (PCS) were measured in both systems. Incorporation of [3H]thymidine and cAMP production were measured in fetal rat calvariae. Production of prostaglandin E2 and I2 and bone resorption, as assessed by release of previously incorporated 45Ca, were measured in mouse parietal bones. The effects of PTHrP and PTH were qualitatively similar. At 96 h CDP in rat calvariae was decreased by PTH at a concentration as low as 0.01 nM, while similar effects were seen with PTHrP at 0.1 nM. Effects on NCP were small, so PCS was reduced. At 24 h [3H]thymidine was not altered, but CDP and PCS were decreased by both PTH and PTHrP. cAMP production was increased in fetal rat calvariae at 30 min. Both PTH and PTHrP increased 45Ca release at low concentrations and prostaglandin production at high concentrations in mouse parietal bones. While PTH was about 10-fold more potent than PTHrP, there was no qualitative difference in the responses. These studies further suggest that PTHrP affects bone through the PTH receptor.