論文 - 詳細
| RRC ID | 18205 |
|---|---|
| 著者 | Takeshita N, Yoshimi E, Hatori C, Kumakura F, Seki N, Shimizu Y. |
| タイトル | Alleviating effects of AS1892802, a Rho kinase inhibitor, on osteoarthritic disorders in rodents. |
| ジャーナル | J Pharmacol Sci |
| Abstract |
The effects of AS1892802, a selective Rho-associated coiled coil kinase (ROCK) inhibitor, on knee cartilage damage and pain behavior were examined in a rat model of osteoarthritis (OA). Monoiodoacetate (MIA) was intraarticularly injected into the right knee joints of rats. ROCK I and II mRNA levels increased in knee joints of MIA-injected rats. Our newly synthesized ROCK inhibitor, AS1892802, was injected into the ipsilateral knee or administered p.o. for 3 weeks. The compound dose-dependently and significantly inhibited of cartilage damage in the tibial plateau in a dose-dependent manner and decreased the weight distribution deficit associated with MIA injection. In addition, the compound also inhibited bradykinin induced pain responses in normal rats. In vitro, the compound could induce chondrocyte differentiation in a chondrogenic cell line and significantly inhibited IL-1β- or bradykinin-induced prostaglandin E(2) production in a synovial cell line. AS1892802 prevents cartilage damage induced by MIA and has analgesic effects in rat pain models, suggesting that AS1892802 may be clinically useful for the treatment of OA.[Supplementary Figure: available only at http://dx.doi.org/10.1254/jphs.10319FP]. |
| 巻・号 | 115(4) |
| ページ | 481-9 |
| 公開日 | 2011-1-1 |
| DOI | 10.1254/jphs.10319fp |
| PII | JST.JSTAGE/jphs/10319FP |
| PMID | 21325780 |
| MeSH | Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology Anti-Inflammatory Agents, Non-Steroidal / therapeutic use* Cell Differentiation / drug effects Cell Line Chondrocytes / physiology Dinoprostone / biosynthesis Disease Models, Animal Dose-Response Relationship, Drug Female Fibroblasts / metabolism Interleukin-1beta Iodoacetic Acid Mice Osteoarthritis, Knee / chemically induced Osteoarthritis, Knee / drug therapy* Osteoarthritis, Knee / prevention & control Pain / chemically induced Pain / drug therapy* Phenylurea Compounds / pharmacology Phenylurea Compounds / therapeutic use* Pyridines / pharmacology Pyridines / therapeutic use* Rabbits Rats Rats, Sprague-Dawley rho-Associated Kinases / antagonists & inhibitors* |
| IF | 2.835 |
| 引用数 | 15 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |