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前列腺素E2通过EP4受体调节人骨关节炎软骨细胞中结缔组织生长因子（CTGF/CCN2）的表达。

Prostaglandin E2 regulates the expression of connective tissue growth factor (CTGF/CCN2) in human osteoarthritic chondrocytes via the EP4 receptor.

作者信息

Masuko Kayo, Murata Minako, Yudoh Kazuo, Shimizu Hiroyuki, Beppu Moroe, Nakamura Hiroshi, Kato Tomohiro

机构信息

Department of Biochemistry, St, Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8511, Japan.

出版信息

BMC Res Notes. 2010 Jan 15;3:5. doi: 10.1186/1756-0500-3-5.

DOI:10.1186/1756-0500-3-5
PMID:20205862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2826353/
Abstract

BACKGROUND

The regulatory mechanisms of the expression of connective tissue growth factor/CCN family member 2 (CTGF/CCN2) in human articular chondrocytes have not been clarified. We investigated the effect of prostaglandin E2 (PGE2) on CTGF/CCN2 expression in chondrocytes.

FINDINGS

Articular cartilage samples were obtained from patients with osteoarthritis (OA) and chondrocytes were isolated and cultured in vitro. Chondrocytes were stimulated with PGE2, PGE receptor (EP)-specific agonists, or interleukin (IL)-1. CTGF expression was analyzed using quantitative polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. The inhibitory effects of EP receptor antagonists (for EP2 and EP4) against PGE2 stimulation were also investigated. Stimulation of chondrocytes with PGE2 or IL-1 significantly suppressed CTGF expression. The suppressive effect of PGE2 was reproduced by EP2/EP4 receptor agonists but not by EP1/EP3 receptor agonists, and was partially blocked by an EP4 receptor antagonist, suggesting that the EP4 receptor has a dominant role.

CONCLUSIONS

PGE2 may be involved in the regulation of CTGF/CCN2 expression in human articular chondrocytes via the EP4 receptor. Elucidation of EP4-mediated signaling in chondrocytes may contribute to a better understanding of the effects of PGE2 in arthritis.

摘要

背景

人类关节软骨细胞中结缔组织生长因子/CCN家族成员2（CTGF/CCN2）表达的调控机制尚未阐明。我们研究了前列腺素E2（PGE2）对软骨细胞中CTGF/CCN2表达的影响。

研究结果

从骨关节炎（OA）患者获取关节软骨样本，分离软骨细胞并进行体外培养。用PGE2、PGE受体（EP）特异性激动剂或白细胞介素（IL）-1刺激软骨细胞。采用定量聚合酶链反应、蛋白质印迹法和酶联免疫吸附测定法分析CTGF表达。还研究了EP受体拮抗剂（针对EP2和EP4）对PGE2刺激的抑制作用。用PGE2或IL-1刺激软骨细胞可显著抑制CTGF表达。EP2/EP4受体激动剂可重现PGE2的抑制作用，而EP1/EP3受体激动剂则不能，且EP4受体拮抗剂可部分阻断该作用，提示EP4受体起主要作用。

结论

PGE2可能通过EP4受体参与调控人类关节软骨细胞中CTGF/CCN2的表达。阐明软骨细胞中EP4介导的信号传导可能有助于更好地理解PGE2在关节炎中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/586ac5962b63/1756-0500-3-5-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/244e005bc7fd/1756-0500-3-5-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/9eaf122bde29/1756-0500-3-5-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/7e07cd286877/1756-0500-3-5-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/b7db6e085316/1756-0500-3-5-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/586ac5962b63/1756-0500-3-5-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/244e005bc7fd/1756-0500-3-5-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/9eaf122bde29/1756-0500-3-5-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/7e07cd286877/1756-0500-3-5-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/b7db6e085316/1756-0500-3-5-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/2826353/586ac5962b63/1756-0500-3-5-5.jpg

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