Prostaglandin E2 Strongly Inhibits Human Osteoclast Formation

• Published in: Endocrinology (Philadelphia) Vol. 146; no. 12; pp. 5204 - 5214
• Main Authors: Take, Ikuko, Kobayashi, Yasuhiro, Yamamoto, Yohei, Tsuboi, Hideki, Ochi, Takahiro, Uematsu, Setsuko, Okafuji, Norimasa, Kurihara, Saburo, Udagawa, Nobuyuki, Takahashi, Naoyuki
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.12.2005
• Subjects: Adult; Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Carrier Proteins - pharmacology; Cell Differentiation - drug effects; Cells, Cultured; Coculture Techniques; Culture Media - pharmacology; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Humans; Lipopolysaccharide Receptors - metabolism; Macrophages - cytology; Male; Membrane Glycoproteins - pharmacology; Mice; Middle Aged; Monocytes - cytology; Monocytes - immunology; Monocytes - metabolism; Nitrobenzenes - pharmacology; Osteoclasts - cytology; Parathyroid Hormone - pharmacology; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Prostaglandin E - metabolism; Sulfonamides - pharmacology; Vertebrates: endocrinology; Osteoarticular system; Human; Arachidonic acid derivatives; Eicosanoid; Prostaglandin E2; Osteoclast; Bone
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2005-0451

Prostaglandin E2 (PGE2) enhances osteoclast formation in mouse macrophage cultures treated with receptor activator of nuclear factor-κB ligand (RANKL). The effects of PGE2 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 PGE2 receptors. PGE2 and PGE1 alcohol (an EP2/4 agonist) stimulated cAMP production in CD14+ cells. In contrast to mouse macrophage cultures, PGE2 and PGE1 alcohol inhibited RANKL-induced human osteoclast formation in CD14+ cell cultures. H-89 blocked the inhibitory effect of PGE2 on human osteoclast formation. These results suggest that the inhibitory effect of PGE2 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. PGE2 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 PGE2 inhibited RANKL-induced osteoclast formation not only in human CD14+ cell cultures, but also in mouse macrophage cultures. These results suggest that PGE2 inhibits human osteoclast formation through the production of an inhibitory factor(s) for osteoclastogenesis of osteoclast precursors.