HUMAN OSTEOCLAST FORMATION FROM BLOOD MONOCYTES, PERITONEAL-MACROPHAGES, AND BONE-MARROW CELLS

Mononuclear precursors of the human osteoclast have been identified in both bone marrow and the circulation in man, but osteoclast membershi p of the mononuclear phagocyte system (MPS) and its precise cellular o ntogeny remain controversial. We isolated human hematopoietic marrow c ells, blood monocytes, and peritoneal macrophages and incubated each o f these cell populations with UMR106 osteoblast-like cells on glass co verslips and den tine slices in both the presence and absence of 1,25 dihydroxyvitamin D-3 (1,25(OH)(2)D-3), macrophage-colony stimulating f actor (M-CSF), and dexamethasone. Cells isolated from peripheral blood and peritoneal dialysis fluid were positive only for monocyte/macroph age markers (CD11a, CD11b, CD14, and HLA-DR) and negative for osteocla st markers [tartrate-resistant acid phosphatase (TRAP), vitronectin re ception (VNR), and calcitonin (CT) receptors and did not form resorpti on pits on dentine slices after 24 hours in culture. Similarly marrow cells did not form resorption pits on dentine slices after 24 hours in culture. However, after 14 days in co-culture with UMR106 cells, in t he presence of 1,25(OH)(2)D-3 and M-CSF, numerous TRAP, CT receptor, a nd VNR-positive multinucleated cells capable of extensive lacunar reso rption were formed in co-cultures of all these preparations. The prese nce of 1,25 (OH)(2)D-3, M-CSF, and UMR106 were absolute requirements f or osteoclast differentiation. It is concluded that precursor cells ca pable of osteoclast differentiation are present in the marrow compartm ent, the monocyte fraction of peripheral blood, and in the macrophage compartment: of extraskeletal tissues and that these cells are capable of differentiating into mature functional osteoclasts. These findings argue in favor of osteoclast membership of the human MPS.