PARATHYROID-HORMONE INDUCES BONE-RESORPTION IN HUMAN PERIPHERAL-BLOODMONONUCLEAR-CELLS

Osteoclasts are known to derive from a macrophage colony-stimulating f actor (M-CSF)-dependent precursor shared with macrophages. Cells capab le of forming osteoclasts are present in peripheral blood. We characte rized this population by incubating human peripheral blood mononuclear cells (PBMCs) with osteoclast-inductive UMR 106 cells, human macropha ge colony stimulating factor (hM-CSF) and parathyroid hormone (PTH) or 1,25(OH)(2)vitamin D3 on slices of devitalised cortical bone. We foun d that PBMCs were capable of substantial bone resorption, to levels co mparable to those of haemopoietic tissue. Cells plated at very low den sities and screened for the presence or absence of excavations reveale d a linear relationship (r = 0.994) between the number of cells plated and the number of excavations formed. The limiting dilution analysis suggested that 1 in every 300-600 plated cells (0.15-0.3% of the PBMC population) had the capacity to resorb bone. The precursor was found i n the rapidly adherent fraction, and typically generated very small nu mbers of excavations, suggesting that it was a relatively mature cell type. Go-cultures of PBMCs with UMR 106 cells would not generate osteo clasts without PTH/1,25(OH)(2)vitamin D3, even with M-CSF, indicating that osteoclast-induction by stromal cells is not attributable to horm onal induction of M-CSF in UMR 106 cells, but that PTH induces some ot her activity, necessary for osteoclast but not macrophage formation, i n UMR 106 cells. Osteoclasts did not form if PTH was omitted in the fi rst few days of the culture period. Thus, osteoclasts appear to form n ot from cells committed to macrophage differentiation, but from a disc rete subpopulation of relatively mature bipotential or osteoclast-comm itted precursors which, in the absence of an osteoclast-inductive stim ulus, become irreversibly lost to the osteoclast lineage.