Effects of lead on osteoclast-like cell formation in mouse bone marrow cell cultures.
To examine an effect of lead (Pb) on the process of osteoclast-like cell formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were formed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration range 2-10 microM, whereas at 40 microM Pb, MNC formation declined. In an 11-day culture period, MNC formation reached a maximum at 5 microM Pb and decreased with increasing concentration of Pb at 10-40 microM. Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an antagonist of prostaglandin E2 (PGE2) receptor. Pb stimulated the production of PGE2 in marrow cell cultures, suggesting that Pb-stimulated MNC formation is dependent on the production of PGE2. 3-Isobutyl-1-methylxanthine potentiated Pb-stimulated MNC formation and 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC formation and verapamil, a calcium channel blocker, depressed it. It is possible that a PGE2-induced increase in the levels of cyclic adenosine 3',5'-monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC formation. From these results, Pb is thought to induce osteoclast-like cell formation by a mechanism involving PGE2 which increases the intracellular levels of cAMP and calcium ions.
Miyahara
T
T
Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Komiyama
H
H
Miyanishi
A
A
Matsumoto
M
M
Xue-Ya
W
W
Takata
M
M
Takata
S
S
Nagai
M
M
Kozuka
H
H
Yokoyama
K
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000502:physiology; D001854:Bone Marrow Cells; D000001:Calcimycin / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010281:Parathyroid Hormone / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D007854:Lead; D000001:Calcimycin; D016048:Dideoxyadenosine; D002116:Calcitonin; D014700:Verapamil; D000242:Cyclic AMP; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin