The metabolism of lead in isolated bone cell populations: interactions between lead and calcium.

Previous studies of lead metabolism in bone organ culture have defined, in part, an exchangeable bone lead compartment regulated by the same ions and hormones that normally control bone cell metabolism. This study was undertaken to further characterize this subcompartment of exchangeable lead and to examine possible interactions between lead and calcium in isolated bone cell populations. Bone cells, derived from mouse calvaria, were enriched for osteoclasts (OC) and osteoblasts (OB) by a sequential collagenase digestion. We found that (1) the uptake of 210Pb by OC cells was rapid, and OC cells had greater avidity for lead, compared to OB cells, at concurrent time points of incubation, (2) OB cells showed very little increase in lead uptake as medium lead concentrations were increased from 6.5 to 65 microM, in contrast, the uptake of lead by OC cells was almost linear, (3) after loading OC cells with 210Pb, significant release of label (approximately 15 to 30%) occurred within short time periods (less than or equal to 2 hr) during incubations in chase medium, (4) parathyroid hormone (PTH) at physiological concentrations effected a marked increase in 210Pb and 45Ca uptake in OC cells, after 5 min of incubation, Pb accumulation into OC cells continued as calcium uptake markedly decreased, (5) this PTH effect on 210Pb uptake was linear over PTH concentrations of 50 to 250 ng/ml, and (6) rising medium concentrations of lead (greater than or equal to 26 microM) markedly enhanced/exaggerated calcium uptake by OC cells, far above that produced by physiological concentrations of PTH. These data indicate that (1) quantitatively, OC cells are the predominant cell type in the metabolism of lead in this in vitro system of OC and OB cell monolayers, (2) mediated incorporation of lead into OC cells occurs and likely involves changes in membrane permeability effected by hormonal stimuli, such as PTH, and (3) modulations in cellular calcium metabolism induced by lead at low concentration may have the potential of disturbing multiple cell functions of different tissues that depend upon calcium as a second messenger.