Prostaglandin E2 strongly inhibits human osteoclast formation
Prostaglandin E2 strongly inhibits human osteoclast formation
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DOI：
10.1210/en.2005-0451
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发表时间：
2005-12-01
期刊：
影响因子：
4.8
通讯作者：
Takahashi, N
中科院分区：
文献类型：
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作者：
Take, I;Kobayashi, Y;Takahashi, N
前列腺素E-2(PGE(2))促进核因子-kappa B受体激活剂(RANKL)处理的小鼠巨噬细胞破骨细胞的形成。体外培养人外周血单个核细胞CD14(+)细胞，观察前列腺素E(2)对破骨细胞形成的影响。CD14(+)细胞在RANKL和巨噬细胞集落刺激因子作用下分化为破骨细胞。CD14(+)细胞表达EP2和EP4，但不表达EP1和EP3，而CD14(+)细胞来源的破骨细胞不表达PGE(2)受体。前列腺素E(2)和前列腺素E(1)乙醇(EP2/4激动剂)刺激CD14(+)细胞产生cAMP。与小鼠巨噬细胞培养相比，PGE(2)和PGE(1)酒精抑制了RANKL诱导的CD14(+)细胞中人破骨细胞的形成。H-89可阻断PGE(2)对人破骨细胞形成的抑制作用。这些结果表明，PGE2对人破骨细胞形成的抑制作用是通过EP2/EP4信号介导的。SAOS4/3细胞在与人外周血单核细胞共培养中支持破骨细胞的形成，以响应甲状旁腺素。PGE(2)可抑制甲状旁腺激素诱导的破骨细胞的形成。相反，NS398(一种环氧合酶2抑制剂)可促进甲状旁腺素诱导的破骨细胞形成。经PGE(2)处理的CD14(+)细胞条件培养液不仅能抑制RANKL诱导的破骨细胞的形成，在人CD14(+)细胞和小鼠巨噬细胞中也能抑制RANKL诱导的破骨细胞的形成。这些结果表明，前列腺素E(2)通过产生破骨细胞前体的破骨形成抑制因子(S)来抑制人破骨细胞的形成。
Prostaglandin E-2 (PGE(2)) enhances osteoclast formation in mouse macrophage cultures treated with receptor activator of nuclear factor-kappa B 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 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. 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.