Inhibition of bone resorption by alpha-difluoromethylornithine may not be mediated by polyamine depletion.
We have examined the effect of alpha-difluoromethylornithine (DFMO) on bone polyamine content and parathyroid hormone (PTH)- and calcitriol-stimulated bone resorption in cultures of neonatal mouse calvaria. Polyamine content in bone homogenates was determined by reverse-phase paired-ion HPLC. Treatment with 5 mM DFMO for 48 h reduced putrescine from 0.4 nmol/bone to nondetectable levels, slightly decreased spermidine, and did not affect spermine. Bone resorption elicited by 48 h of treatment with PTH or calcitriol was inhibited by concentrations of DFMO greater than or equal to 5 mM added 48 h prior to hormone. This observation supported the concept that polyamines may play a role in bone resorption. However, other observations cast uncertainty on this conclusion. Measurement of calvarial polyamine content at 2 h intervals revealed no increase in endogenous polyamines for up to 10.5 h after calcitriol addition. Although addition of putrescine restored bone polyamine content, exogenous polyamines failed to reverse the inhibitory effects of DFMO on calcitriol-stimulated resorption. These results suggest that a mechanism other than depletion of polyamines could be contributing to the inhibitory effect of DFMO on resorption.
Lucas
R C
RC
Department of Pharmacology, Northwestern University, Chicago, IL 60611.
Seidenfeld
J
J
Krieger
N S
NS
Stern
P H
PH
D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D046508:Culture Techniques; D000518:Eflornithine / Q000627:therapeutic use*; D051379:Mice; D009952:Ornithine / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D010281:Parathyroid Hormone / Q000494:pharmacology
D015317:Biogenic Polyamines; D002132:Calcium Radioisotopes; D065108:Ornithine Decarboxylase Inhibitors; D010281:Parathyroid Hormone; D009952:Ornithine; D002117:Calcitriol; D002118:Calcium; D000518:Eflornithine