Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells
Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells
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DOI：
10.1002/jcp.20031
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发表时间：
2004-09-01
影响因子：
5.6
通讯作者：
Morita, I
中科院分区：
文献类型：
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作者：
Arikawa, T;Omura, K;Morita, I
环氧合酶(COX)-2通常被认为是一种诱导酶，它产生花生四烯酸到前列腺素E2 (PGE2)，其调节骨代谢。在这里，我们研究了COX异构体在人间充质干细胞中的表达和作用。人间充质干细胞组成性地表达COX-2和COX-1， PGE2的分泌被COX-2特异性抑制剂NS-398完全抑制。人间充质干细胞分泌的PGE2水平明显高于从间充质干细胞分化而来的成骨细胞。间充质干细胞中PGE2的高产量是由于早期生长反应因子-1 （Egr-1）调节的膜相关PGE合成酶（mPGES）的高表达。NS-398处理人间充质干细胞抑制骨形态发生蛋白2 （BMP-2）的表达。NS-398对BMP-2的抑制作用被EP4受体激动剂和PGE2所消除。此外，BMP-2的表达被EP4受体拮抗剂抑制。这些数据表明COX-2产生的PGE2通过结合EP4受体增加BMP-2的表达。(C) 2004 Wiley-Liss, Inc。
Cyclooxygenase (COX)-2 is generally known as an inducible enzyme, and it produces arachidonic acid to prostaglandin E2 (PGE2), which modulates bone metabolism. Here, we investigated the expression and role of COX isomers in human mesenchymal stem cells. Human mesenchymal stem cells constitutively expressed COX-2 as well as COX-1, and secretion of PGE2 was completely inhibited by NS-398, a specific inhibitor of COX-2. Levels of secreted PGE2 were strikingly higher in human mesenchymal stem cells than in osteoblastic cells differentiated from the mesenchymal cells. This higher production of PGE2 in mesenchymal stem cells was due to higher expression of membrane-associated PGE synthase (mPGES) regulated by early growth response factor-1 (Egr-1). Treatment of human mesenchymal stem cells with NS-398 suppressed expression of bone morphogenetic protein-2 (BMP-2). The suppression of BMP-2 by NS-398 was abrogated by an EP4 receptor agonist as well as by PGE2. Moreover, BMP-2 expression was suppressed by an EP4 receptor antagonist. These data indicate that PGE2 produced by COX-2 increases BMP-2 expression via binding the EP4 receptor. (C) 2004 Wiley-Liss, Inc.