title: Prostaglandin E2 strongly inhibits human osteoclast formation.
abstract: Prostaglandin E(2) (PGE(2)) enhances osteoclast formation in mouse macrophage cultures treated with receptor activator of nuclear factor-kappaB ligand (RANKL). The effects of PGE(2) on human osteoclast formation were examined in cultures of CD14(+) cells prepared from human peripheral blood mononuclear cells. CD14(+) cells differentiated into osteoclasts in the presence of RANKL and macrophage colony-stimulating factor. CD14(+) cells expressed EP2 and EP4, but not EP1 or EP3, whereas CD14(+) cell-derived osteoclasts expressed none of the PGE(2) receptors. PGE(2) and PGE(1) alcohol (an EP2/4 agonist) stimulated cAMP production in CD14(+) cells. In contrast to mouse macrophage cultures, PGE(2) and PGE(1) alcohol inhibited RANKL-induced human osteoclast formation in CD14(+) cell cultures. H-89 blocked the inhibitory effect of PGE(2) on human osteoclast formation. These results suggest that the inhibitory effect of PGE(2) on human osteoclast formation is mediated by EP2/EP4 signals. SaOS4/3 cells have been shown to support human osteoclast formation in cocultures with human peripheral blood mononuclear cells in response to PTH. PGE(2) inhibited PTH-induced osteoclast formation in cocultures of SaOS4/3 cells and CD14(+) cells. Conversely, NS398 (a cyclooxygenase 2 inhibitor) enhanced osteoclast formation induced by PTH in the cocultures. The conditioned medium of CD14(+) cells pretreated with PGE(2) inhibited RANKL-induced osteoclast formation not only in human CD14(+) cell cultures, but also in mouse macrophage cultures. These results suggest that PGE(2) inhibits human osteoclast formation through the production of an inhibitory factor(s) for osteoclastogenesis of osteoclast precursors.
authors.affiliation: Graduate School of Oral Medicine, Matsumoto Dental University, Nagano, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Take
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsuboi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochi
authors.forename: Setsuko
authors.initials: S
authors.lastname: Uematsu
authors.forename: Norimasa
authors.initials: N
authors.lastname: Okafuji
authors.forename: Saburo
authors.initials: S
authors.lastname: Kurihara
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D003470:Culture Media; D016861:Cyclooxygenase Inhibitors; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D009578:Nitrobenzenes; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018078:Receptors, Prostaglandin E; D013449:Sulfonamides; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D015232:Dinoprostone