In vitro bone resorption is dependent on physiological concentrations of zinc.
The addition of physiological concentrations of zinc (25-200 (microg/dL) to Dulbecco's Modified Eagle's Medium containing tibiae from 19-d chick embryos resulted in a concentration-dependent increase in tibial content of tartrate-resistant acid phosphatase (TRAP) and an increase in bone resorption, as measured by tibial calcium release. This increase in bone resorption was additive to the resorptive effect resulting from the addition of 10(-9)-10(-7) M parathyroid hormone (PTH), but was not additive to similar effects produced by the addition of 10(-9)-10(-7) M prostaglandin E2 (PGE2). An inhibitor of prostaglandin synthesis, flurbiprofen (10[-6] M), did not influence the effect of zinc on bone resorption. However, the addition of 2,6-pyridinedicarboxylic acid (10[-3] M, 2,6-PDCA), a chelator of zinc, did attenuate the effects of zinc, as did the addition of an inhibitor of DNA replication (hydroxyurea, 10[-3] M). Hydroxyurea also attenuated the bone resorptive response to PGE2, but had no influence on the effects of PTH. These results indicate that physiological concentrations of zinc alter bone resorptive rates in vitro by a mechanism that is dependent on DNA replication.
Chen
D
D
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, KY 40292, USA.
Waite
L C
LC
Pierce
W M
WM
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002642:Chick Embryo; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D015232:Dinoprostone; D005480:Flurbiprofen / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010281:Parathyroid Hormone; D010848:Picolinic Acids / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D013977:Tibia / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*
D002614:Chelating Agents; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D019384:Nucleic Acid Synthesis Inhibitors; D010281:Parathyroid Hormone; D010848:Picolinic Acids; D005480:Flurbiprofen; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D015032:Zinc; D015232:Dinoprostone; D002118:Calcium; C004860:dipicolinic acid; D006918:Hydroxyurea