Parathyroid hormone induces bone resorption in human peripheral blood mononuclear cells

Osteoclasts are known to derive from a macrophage colony-stimulating factor (M-CSF)-dependent precursor shared with macrophages. Cells capable of forming osteoclasts are present in peripheral blood. We characterized this population by incubating human peripheral blood mononuclear cells (PBMCs) with osteoclast-inductive UMR 106 cells, human macrophage colony stimulating factor (hM-CSF) and parathyroid hormone (PTH) or 1.25(OH)2 vitamin D3 on slices of devitalised cortical bone. We found that PBMCs were capable of substantial bone resorption, to levels comparable to those of haemopoietic tissue. Cells plated at very low densities and screened for the presence or absence of excavations revealed 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 in the rapidly adherent fraction, and typically generated very small numbers of excavations, suggesting that it was a relatively mature cell type. Co-cultures of PBMCs with UMR 106 cells would not generate osteoclasts without PTH/1.25(OH)2 vitamin D3, even with M-CSF, indicating that osteoclast-induction by stromal cells is not attributable to hormonal induction of M-CSF in UMR 106 cells, but that PTH induces some other activity, necessary for osteoclast but not macrophage formation, in UMR 106 cells. Osteoclasts did not form if PTH was omitted in the first few days of the culture period. Thus, osteoclasts appear to form not from cells committed to macrophage differentiation, but from a discrete subpopulation of relatively mature bipotential or osteoclast-committed precursors which, in the absence of an osteoclast-inductive stimulus, become irreversibly lost to the osteoclast lineage.