{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:11:40Z","timestamp":1762323100905,"version":"3.33.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,12,12]],"date-time":"2005-12-12T00:00:00Z","timestamp":1134345600000},"content-version":"vor","delay-in-days":3236,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1997,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Objective<\/jats:italic>. To study, in vivo, the therapeutic effectiveness of tenidap, an antirheumatic drug, on the progression of lesions in an experimental osteoarthritis (OA) dog model. The action of tenidap on the activity and expression of metalloproteases in cartilage, as well as on the bioactivity of interleukin\u20101 (IL\u20101) in synovial fluid, was determined.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>. The anterior cruciate ligament of the right stifle joint of 20 mongrel dogs was sectioned through a stab wound. Dogs were divided into 3 groups: group I (n = 7) received no treatment, group II (n = 6) was treated with oral omeprazole (20 mg\/day), and group III (n = 7) received oral omeprazole (20 mg\/day) and a therapeutic dosage of oral tenidap (3 mg\/kg twice daily). Four weeks following surgery, the untreated dogs (group I) were killed, and drug treatments were begun for the other dogs (groups II and III). These dogs received medication for 8 weeks (weeks 4\u201312) and then were killed. Evaluations were made of the incidence and size of osteophytes as well as of the size and grade of cartilage erosions on both the condyles and plateaus. Histologic examination of the severity of the cartilage lesions and synovial inflammation was also performed. Activity levels of collagenase, stromelysin, and gelatinase as well as collagenase\u20101, collagenase\u20103, and stromelysin\u20101 messenger RNA were determined in the cartilage. The level of IL\u20101 activity in the synovial fluid was also measured.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. Among the dogs with OA, lesions were more severe at 12 weeks than at 4 weeks. Group III (tenidap\u2010treated) dogs had a slightly reduced incidence of osteophytes compared with the group II (12\u2010week OA) dogs (71% versus 100%), and the size of the osteophytes was significantly diminished (mean \u00b1 SEM 1.75 \u00b1 0.69 mm versus 4.38 \u00b1 0.64 mm). Macroscopically, tenidap decreased the size (condyles 6.00 \u00b1 2.18 mm<jats:sup>2<\/jats:sup>versus 21.08 \u00b1 6.70 mm<jats:sup>2<\/jats:sup>, plateaus 15.50 \u00b1 4.77 mm<jats:sup>2<\/jats:sup>versus 35.0 \u00b1 3.64 mm<jats:sup>2<\/jats:sup>) and the grade (condyles 0.57 \u00b1 0.20 versus 1.17 \u00b1 0.21, plateaus 1.07 \u00b1 0.22 versus 2.00 \u00b1 0.25) of the cartilage lesions compared with the 12\u2010week OA dogs. At the histologic level, the severity of cartilage lesions was also decreased in the tenidap\u2010treated dogs versus the 12\u2010week OA dogs, both on the condyles (3.43 \u00b1 0.54 versus 5.55 \u00b1 0.38) and on the plateaus (3.39 \u00b1 0.35 versus 5.54 \u00b1 0.60). All 3 OA groups showed a significant and similar level of synovial inflammation. Tenidap markedly decreased collagenase, stromelysin, and gelatinase activity, as well as the level of expression of collagenase\u20103 in the cartilage. Interestingly, the activity level of IL\u20101 in synovial fluid was also significantly reduced in the tenidap\u2010treated dogs.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>. Tenidap markedly reduced the severity of OA lesions, indicating the effect of this drug in decreasing the progression of disease. It appears that the drug acts by reducing the activity and\/or expression of metalloproteases in cartilage, a process known to play a major role in the pathophysiology of OA lesions. This effect could be mediated by the suppressive effect of tenidap on IL\u20101 activity.<\/jats:p>","DOI":"10.1002\/art.1780400213","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T12:24:20Z","timestamp":1171455860000},"page":"284-294","source":"Crossref","is-referenced-by-count":24,"title":["Effects of tenidap on the progression of osteoarthritic lesions in a canine experimental model. 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