1,25-dihydroxyvitamin D3 and prostaglandin E2 act directly on circulating human osteoclast precursors

1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) and prostaglandin E-2 (PGE(2)) are known to influence osteoclast formation indirectly through their effects on osteoblasts. To determine whether 1,25(OH)(2)D-3 and PGE(2) also have a direct effect on circulating osteoclast precursors, these factors were added to long-term cultures of human peripheral blood mononuclear cells (PBMCs) in the presence of osteoprotegerin ligand and macrophage colony-stimulating factor (M-CSF) (+/-dexamethasone). The number of TRAP(+) and VNR+ multinucleated cells and the area of lacunar resorption were decreased when 1,25(OH)(2)D-3 alone was added. A marked increase in resorption pit formation was noted when the combination of 1,25(OH)(2)D-3 and dexamethasone was added to PBMC cultures. Dose-dependent inhibition of osteoclast formation and lacunar resorption was seen when PGE(2) was added to PBMC cultures in both the presence and the absence of dexamethasone. Thus, 1,25(OH)(2)D-3 and PGE(2) not only influence osteoclast formation in the presence of bone stromal cells but also act directly on circulating osteoclast precursors to influence osteoclast differentiation. (C) 1999 Academic Press.