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 ce ll formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were form ed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration rang e 2-10 mu M, whereas at 40 mu M Pb, MNC formation declined. In an 11-d ay culture period, MNC formation reached a maximum at 5 mu M Pb and de creased with increasing concentration of Pb at 10-40 mu M. Pb-stimulat ed MNC formation was inhibited by both indomethacin and SC19220, an an tagonist of prostaglandin E(2) (PGE(2)) receptor. Pb stimulated the pr oduction of PGE(2) in marrow cell cultures, suggesting that Pb-stimula ted MNC formation is dependent on the production of PGE(2). 3-Isobutyl -1-methylxanthine potentiated Pb-stimulated MNC formation and 2',5'-di deoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A cal cium ionophore A23187 increased Pb-induced MNC formation and verapamil , a calcium channel blocker, depressed it. It is possible that a PGE(2 )-induced increase in the levels of cyclic adenosine 3',5'-monophospha te (cAMP) and calcium ions in marrow cells is involved in Pb-induced M NC formation. Pb and parathyroid hormone showed a synergistic stimulat ion on MNC formation. From these results, Pb is thought to induce oste oclast-like cell formation by a mechanism involving PGE(2) which incre ases the intracellular levels of cAMP and calcium ions.