On the role of polyamines in bone resorption induced by parathyroid hormone.
In order to elucidate the possible role of polyamines in the mobilization of mineral from long-term bone cultures stimulated with parathyroid hormone we have measured the activity of ornithine decarboxylase in osteoblasts, the levels of polyamines in calvarial bone and determined the effect of added polyamines and inhibitors of polyamine biosynthesis on calcium mobilization. Parathyroid hormone (10 nmol l-1) stimulated omithine decarboxylase activity by approximately 50% in both cultured bone cells of osteoblastic phenotype, UMR 106 and in mouse calvarial osteoblast-like cells. In mouse calvaria the levels of putrescine and spermidine were increased by parathyroid hormone after 24 hours. The levels of spermine were very low and were unchanged by parathyroid hormone. The two polyamine synthesis inhibitors alpha-difluoromethylornithine (DFMO; 2 mmol l-1) and methylglyoxal-bis-guanylhydrazone (MGBG; 50 mu mol l-1) did not significantly affect the mobilization of 45Ca from parathyroid hormone-stimulated bones. All three polyamines, putrescine, spermidine and spermine, inhibited the mobilization of 45Ca induced by parathyroid hormone in a dose-dependent manner. The inhibition induced by putrescine was reversible. In summary, we have shown that parathyroid hormone increases the accumulation of polyamines in bone, but the effect is small. Furthermore, inhibition of polyamine biosynthesis does not reduce parathyroid hormone-induced mineral mobilization and the addition of polyamines leads to a reduced rather than a stimulated mineral mobilization. Thus, polyamines do not seem to be critically involved in the changes in bone resorption induced by parathyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
Ljunggren
O
O
Department of Oral Pathology, Umeå University, Sweden.
Fredholm
B B
BB
Lerner
U H
UH
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001862:Bone Resorption / Q000139:chemically induced / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D000518:Eflornithine / Q000494:pharmacology; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010281:Parathyroid Hormone / Q000633:toxicity*; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012886:Skull / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D010281:Parathyroid Hormone; D011073:Polyamines; D013096:Spermine; D009955:Ornithine Decarboxylase; D002118:Calcium; D013095:Spermidine; D000518:Eflornithine