α-Difluoromethylornithine inhibits bone resorption in vitro without decreasing β-glucuronidase release

Paula H. Stern*, Rita C. Lucas, Jerome Seidenfeld

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Our previous studies suggested that the ornithine decarboxylase inhibitor α-difluoromethylornithine (DFMO) inhibits bone resorption by mechanisms that are independent of polyamine depletion. To determine whether DFMO prevents calcitriol-stimulated bone resorption by acting at a step before or after osteoclast activation, we compared the effects of DFMO on release of calcium and β-glucuronidase from cultured neonatal mouse calvaria. DFMO, at concentrations of 7.5-20 mM, inhibited release of calcium from calcitriol-stimulated calvaria but failed to inhibit the calcitriol-stimulated increase in β-glucuronidase secretion. In contrast, ornithine, putrescine, spermidine, and spermine, at concentrations with effects on resorption comparable to those of DFMO, inhibited the effects of calcitriol on both calcium and β-glucuronidase release. NaF (0.2 mM), like DFMO, inhibited calcitriol-stimulated calcium release without affecting medium β-glucuronidase activity, whereas elevated phosphate (3 mM) inhibited both activities. The results suggest that DFMO, over the concen-tration range studied, inhibits calcium release by making the matrix resistant to resorption rather than by acting at a cellular locus.

Original languageEnglish (US)
Pages (from-to)557-562
Number of pages6
JournalMolecular pharmacology
Volume39
Issue number4
StatePublished - Apr 1991

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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