Open Access Research article

Prostaglandin E2 receptor type 2-selective agonist prevents the degeneration of articular cartilage in rabbit knees with traumatic instability

Hiroto Mitsui13, Tomoki Aoyama14*, Moritoshi Furu12, Kinya Ito13, Yonghui Jin1, Takayuki Maruyama5, Toshiya Kanaji5, Shinsei Fujimura5, Hikaru Sugihara5, Akio Nishiura5, Takanobu Otsuka3, Takashi Nakamura2 and Junya Toguchida126

Author affiliations

1 Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

2 Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

3 Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

4 Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

5 Ono Pharmaceutical Co. Ltd.,3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan

6 Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

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Citation and License

Arthritis Research & Therapy 2011, 13:R146  doi:10.1186/ar3460

Published: 14 September 2011

Abstract

Introduction

Osteoarthritis (OA) is a common cause of disability in older adults. We have previously reported that an agonist for subtypes EP2 of the prostaglandin E2 receptor (an EP2 agonist) promotes the regeneration of chondral and osteochondral defects. The purpose of the current study is to analyze the effect of this agonist on articular cartilage in a model of traumatic degeneration.

Methods

The model of traumatic degeneration was established through transection of the anterior cruciate ligament and partial resection of the medial meniscus of the rabbits. Rabbits were divided into 5 groups; G-S (sham operation), G-C (no further treatment), G-0, G-80, and G-400 (single intra-articular administration of gelatin hydrogel containing 0, 80, and 400 μg of the specific EP2 agonist, ONO-8815Ly, respectively). Degeneration of the articular cartilage was evaluated at 2 or 12 weeks after the operation.

Results

ONO-8815Ly prevented cartilage degeneration at 2 weeks, which was associated with the inhibition of matrix metalloproteinase-13 (MMP-13) expression. The effect of ONO-8815Ly failed to last, and no effects were observed at 12 weeks after the operation.

Conclusions

Stimulation of prostaglandin E2 (PGE2) via EP2 prevents degeneration of the articular cartilage during the early stages. With a system to deliver it long term, the EP2 agonist could be a new therapeutic tool for OA.

Keywords:
prostaglandin E2; EP2; ONO-8815Ly; osteoarthritis; ACLMT