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Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells

✍ Scribed by Toshitaka Arikawa; Ken Omura; Ikuo Morita

Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
209 KB
Volume
200
Category
Article
ISSN
0021-9541

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✦ Synopsis

Abstract

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. © 2004 Wiley‐Liss, Inc.

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