前列腺素（PG）E受体亚型EP4在前列腺素E2诱导的小鼠骨髓细胞形成破骨细胞样细胞过程中的重要作用。

Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2.

作者信息

Ono K, Akatsu T, Murakami T, Nishikawa M, Yamamoto M, Kugai N, Motoyoshi K, Nagata N

机构信息

Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.

出版信息

J Endocrinol. 1998 Sep;158(3):R1-5. doi: 10.1677/joe.0.158r001.

DOI:10.1677/joe.0.158r001

PMID:9846175

Abstract

Of various PGs, PGE1 and PGE2 are shown to be the most potent stimulators of osteoclastogenesis in vitro. PGE receptors have been classified into four subtypes, EP1-EP4. Little is known about PGE receptors functioning in bone cells. In this study, using mouse marrow culture, we investigated which PGE receptors are important in osteoclast-like cell (OCL) formation induced by PGE. 11-deoxy-PGE1 (EP2, EP3 and EP4 agonist) stimulated OCL formation potently. Butaprost (EP2 agonist) stimulated it slightly, while sulprostone (EP1 and EP3 agonist) and ONO-AP-324-01 (EP3 agonist) did not. AH23848B (EP4 antagonist) inhibited PGE2-induced OCL formation in a dose-dependent manner. The expression of EP4 mRNA in mouse bone marrow was confirmed by RT-PCR. The results indicate an important role of EP4 in PGE2-induced OCL formation in marrow cultures and suggest therapeutic potential of EP4 antagonists in some clinical conditions with accelerated bone resorption.

摘要

在各种前列腺素（PGs）中，PGE1和PGE2被证明是体外破骨细胞生成最有效的刺激物。PGE受体已被分为四种亚型，即EP1-EP4。关于PGE受体在骨细胞中的功能知之甚少。在本研究中，我们使用小鼠骨髓培养，研究了哪些PGE受体在PGE诱导的破骨样细胞（OCL）形成中起重要作用。11-脱氧-PGE1（EP2、EP3和EP4激动剂）强烈刺激OCL形成。布他前列素（EP2激动剂）轻微刺激OCL形成，而舒前列素（EP1和EP3激动剂）和ONO-AP-324-01（EP3激动剂）则无此作用。AH23848B（EP4拮抗剂）以剂量依赖性方式抑制PGE2诱导的OCL形成。通过逆转录聚合酶链反应（RT-PCR）证实了小鼠骨髓中EP4 mRNA的表达。结果表明EP4在骨髓培养中PGE2诱导的OCL形成中起重要作用，并提示EP4拮抗剂在某些骨吸收加速的临床病症中具有治疗潜力。