Prostaglandin E2 Strongly Inhibits Human Osteoclast Formation

Author:

Take Ikuko,Kobayashi Yasuhiro,Yamamoto Yohei,Tsuboi Hideki,Ochi Takahiro,Uematsu Setsuko,Okafuji Norimasa,Kurihara Saburo,Udagawa Nobuyuki,Takahashi Naoyuki

Abstract

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.

Publisher

The Endocrine Society

Subject

Endocrinology

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