| 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
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
