TY - JOUR
T1 - α-Difluoromethylornithine inhibits bone resorption in vitro without decreasing β-glucuronidase release
AU - Stern, Paula H.
AU - Lucas, Rita C.
AU - Seidenfeld, Jerome
PY - 1991/4
Y1 - 1991/4
N2 - 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.
AB - 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.
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U2 - 10.1016/s0026-895x(25)11021-3
DO - 10.1016/s0026-895x(25)11021-3
M3 - Article
C2 - 2017155
AN - SCOPUS:0025774554
SN - 0026-895X
VL - 39
SP - 557
EP - 562
JO - Molecular pharmacology
JF - Molecular pharmacology
IS - 4
ER -