Prostaglandin E2 (PGE2) increases the number of rat bone marrow osteogenic stromal cells (BMSC) via binding the EP4 receptor, activating sphingosine kinase and inhibiting caspase activity

被引:54
作者
Weinreb, M. [1 ]
Shamir, D.
Machwate, M.
Rodan, G. A.
Harada, S.
Keila, S.
机构
[1] Tel Aviv Univ, Dept Oral Biol, Maurice & Gabriela Goldschleger Sch Dent Med, IL-69978 Tel Aviv, Israel
[2] Merck Res Labs, Dept Bone Biol, West Point, PA USA
来源
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS | 2006年 / 75卷 / 02期
关键词
D O I
10.1016/j.plefa.2006.06.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Prostaglandin E-2 (PGE(2)) is bone-anabolic, i.e. stimulates bone formation and increases bone mass. In this study, we explored possible intracellular mechanisms of its increase of osteogenic cells in rat bone marrow. Adherent rat bone marrow cells were counted after 12-48 h or cultured for 21 days and mineralized nodules were counted. Also, apoptosis of marrow cells was measured after in vivo PGE(2) injection. PGE(2) (100 nM) increased 2-3 fold the number of adherent BMSC, an effect which was mediated via binding the EP4 receptor since it was mimicked by forskolin and 11-deoxy-prostaglandin E-1 (PGE(1)) and was blocked by DDA and L-161982 (EP4 antagonist). PGE(2) stimulated sphingosine kinase (SPK) activity since its effects were blocked by DMS (SPK inhibitor) and mimicked by SPP (SPK product). PGE(2) reduced the activity of caspase-3 and -8 in BMSC and their inhibitors increased BMSC number and nodule formation. In vivo, PGE(2) prevented the increase in the apoptosis of bone marrow cells caused by indomethacin. We propose that PGE(2) exerts an anti-apoptotic effect on BMSC, thereby increasing their number and subsequent osteoblastic differentiation. Such an effect could explain how PGE(2) stimulates bone formation in vivo. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:81 / 90
页数:10
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