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Prevention of progressive joint destruction in collagen‐induced arthritis in rats by a novel matrix metalloproteinase inhibitor, FR255031
Author(s) -
Ishikawa Takeshi,
Nishigaki Fusako,
Miyata Susumu,
Hirayama Yoshitaka,
Minoura Kyoko,
Imanishi Junko,
Neya Masahiro,
Mizutani Tsuyoshi,
Imamura Yoshimasa,
Naritomi Yoichi,
Murai Hidetsugu,
Ohkubo Yoshitaka,
Kagayama Akira,
Mutoh Seitaro
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706054
Subject(s) - collagenase , gelatinases , matrix metalloproteinase , arthritis , gelatinase , matrix metalloproteinase inhibitor , type ii collagen , cartilage , intradermal injection , chemistry , medicine , endocrinology , pannus , synovial membrane , cartilage oligomeric matrix protein , osteoarthritis , pathology , immunology , biochemistry , anatomy , enzyme , alternative medicine
1 FR255031 (2‐[(7 S )‐7‐[5‐(4‐ethylphenyl)‐2‐thienyl]‐1,1‐dioxido‐4‐(2‐pyridinylcarbonyl)hexahydro‐1,4‐thiazepin‐7‐yl]‐ N ‐hydroxyacetamide) is a novel synthetic matrix metalloproteinase (MMP) inhibitor that inhibits human collagenases (MMP‐1, MMP‐8 and MMP‐13), gelatinases (MMP‐2 and MMP‐9) and membrane type 1 MMP (MT1‐MMP/MMP‐14). FR255031 also inhibits rat collagenase and gelatinase. We studied the effect of FR255031 and Trocade, an inhibitor of collagenase and MMP‐14, on a rat collagen‐induced arthritis (CIA) model. 2 Rat CIA was induced by intradermal injection of type II collagen (IIC) and oral administration of FR255031 or Trocade was performed for 28 days. Body weight loss, hind paw swelling, elevation of serum anti‐IIC antibody, and histological and radiographic scores were evaluated. 3 FR255031 markedly inhibited cartilage degradation in a dose‐dependent manner in the CIA model, but Trocade failed to prevent the degradation. 4 FR255031 at a dose of 100 mg kg −1 also had statistically significant effects on bone destruction and pannus formation and on the recovery of body weight loss on day 28. 5 These results indicate that FR255031 is effective for rat CIA, especially on joint cartilage destruction. These data suggest that as well as collagenases or MT‐MMP, gelatinases are also involved in joint destruction in arthritis.British Journal of Pharmacology (2005) 144 , 133–143. doi: 10.1038/sj.bjp.0706054