Prostaglandin E2 strongly inhibits human osteoclast formation.
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.
Take
Ikuko
I
Graduate School of Oral Medicine, Matsumoto Dental University, Nagano, Japan.
Kobayashi
Yasuhiro
Y
Yamamoto
Yohei
Y
Tsuboi
Hideki
H
Ochi
Takahiro
T
Uematsu
Setsuko
S
Okafuji
Norimasa
N
Kurihara
Saburo
S
Udagawa
Nobuyuki
N
Takahashi
Naoyuki
N
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
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