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Development of the treatment for cartilage regeneration by a prostanoid signal-acting material

通过前列腺素信号作用材料开发软骨再生治疗方法

基本信息

批准号：
16390437
负责人：
TOGUCHIDA Junya
金额：
$ 8.64万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390437/
关键词：
articular cartilage Prostaglandin E2 EP2 receptor mesenchymal stem cell cartilage regeneration プロスタグランデインE2 PGE2 EP2 軟骨修復マイクロアレイ

项目摘要

The effects of EP2 agonists for the treatment of articular cartilage defects were investigated by in vivo experiments. Full thickness cartilage defects (5mm in diameter and 5mm depth) and surface cartilage defects (5mm in dianeter) were created in the patello-femoral joint surface of the distal portion of femurs of rabbits. Histological examination was performed immediately after the operation, which confirmed the porper procedure to creat intended defects for each model. Treatment was carried out using EP2 agonists slow-releasing materials (PLGA+gelatin gel, 5mm in diameter and 5mm height), which was placed in the defect in the case of full thickness defect model and adjacet to infrapatellar fat pad in the case of surface defect model. The amount of EP2 agonist were either 20mg, 80mg, or 800mg. Animals were sacrified at four weeks after operation, and the defects were examined histologically. In the case of full thickness model, the defect was filled with tissues, which mainly composed of safranion-O negative spindel cells. The proliferation of cartilage cells were observed at the junction facing to residual normal articular cartialge, the amount of which depended on the dose of EP2 agonists. In the surface defect model, the defect was filled with regenerated chondrocytes, which were positive for safaranin-O staining. There were many lacunae containing two cells, indicating the active proliferation of articular chondrocytes. These resultis suggested that PGE2 signal through EP2 stimulated proliferation of articular cartilage cells, and that combined with a proper drug-delivery system, EP2 agonists will be promising therapeutic materials for damaged articular cartilages, which have been regarded not to have a regenerative potency.

通过体内实验研究了EP2激动剂治疗关节软骨缺损的效果。在兔股骨远端髌股关节面制作全层软骨缺损（直径5mm，深度5mm）和表面软骨缺损（直径5mm）。手术后立即进行组织学检查，证实了为每个模型创建预期缺陷的适当程序。采用EP2激动剂缓释材料（PLGA+明胶凝胶，直径5mm，高度5mm）进行治疗，如果是全层缺损模型，则将其放置在缺损内；如果是表面缺损模型，则将其置于髌下脂肪垫附近。 EP2激动剂的量为20mg、80mg或800mg。术后4周处死动物，并对缺陷进行组织学检查。在全层模型的情况下，缺损处充满组织，主要由番红花-O阴性纺锤体细胞组成。在面向残留正常关节软骨的交界处观察到软骨细胞的增殖，其数量取决于EP2激动剂的剂量。在表面缺损模型中，缺损处充满了再生软骨细胞，番红素-O 染色呈阳性。存在许多含有两个细胞的腔隙，表明关节软骨细胞增殖活跃。这些结果表明，PGE2信号通过EP2刺激关节软骨细胞的增殖，并且与适当的药物递送系统相结合，EP2激动剂将成为有希望的治疗受损关节软骨的材料，而受损关节软骨一直被认为不具有再生能力。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Methylation in the core-promoter region of the chondromodulin-I gene determines the cell-specific expression by regulating the binding of transcriptional activator Sp3

DOI：
10.1074/jbc.m401273200
发表时间：
2004-07-02
期刊：
JOURNAL OF BIOLOGICAL CHEMISTRY
影响因子：
4.8
作者：
Aoyama, T;Okamoto, T;Toguchida, J
通讯作者：
Toguchida, J

Expression of the chondromodulin-I gene in chondrosarcomas

DOI：
10.1016/j.canlet.2003.09.015
发表时间：
2004-02-10
期刊：
CANCER LETTERS
影响因子：
9.7
作者：
Aoyama, T;Okamoto, T;Toguchida, J
通讯作者：
Toguchida, J

Expression of the cadherin-11 gene is a discriminative factor between articular and growth plate chondrocytes.

DOI：
10.1016/j.joca.2005.10.008
发表时间：
2006-04
期刊：
Osteoarthritis and cartilage
影响因子：
7
作者：
T. Matsusaki;T. Aoyama;K. Nishijo;T. Okamoto;T. Nakayama;T. Nakamura;J. Toguchida
通讯作者：
T. Matsusaki;T. Aoyama;K. Nishijo;T. Okamoto;T. Nakayama;T. Nakamura;J. Toguchida

PGE2 signal through EP2 promotes the growth of articular chondrocytes