{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:47:00Z","timestamp":1791312420367,"version":"4.3.1"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,12,12]],"date-time":"2005-12-12T00:00:00Z","timestamp":1134345600000},"content-version":"vor","delay-in-days":3389,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective<\/jats:italic>\n                    . To investigate the in vivo effect of recombinant human interleukin\u20101 receptor antagonist (rHuIL\u20101Ra) on the development of lesions and the expression of metalloproteases in the canine experimental osteoarthritis (OA) model.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods<\/jats:italic>\n                    . The right anterior cruciate ligament was sectioned percutaneously in 3 groups of dogs. The control group (n = 5) received an intraarticular injection of sterile physiologic saline (1 ml) twice weekly for 4 weeks starting on the day of surgery. The remaining 2 groups received intraarticular injections of either 2 mg (n = 6) or 4 mg (n = 5) rHuIL\u20101Ra in 1 ml of physiologic saline according to the same schedule as the first group. All dogs were killed 4 weeks after surgery. The macroscopic appearance of femoral condyle osteophytes and the size and severity of cartilage lesions on femoral condyles and tibial plateaus were evaluated, as were the histologic features of cartilage and synovial membrane. Levels of collagenase\u20101 and stromelysin\u20101 messenger RNA expression in cartilage and synovium were determined by Northern blotting.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Results<\/jats:italic>\n                    . Recombinant human IL\u20101Ra exerted a dose\u2010dependent protective effect on the development of osteophytes and cartilage lesions in vivo. Treatment with rHuIL\u20101Ra reduced the incidence (saline\u2010treated group 70%, 2 mg rHuIL\u20101Ra\u2013treated group 42%, 4 mg rHuIL\u20101Ra\u2013treated group 20%) and size (saline\u2010treated group 2.3 \u00b1 0.7 mm [mean \u00b1 SEM], 2 mg rHuIL\u20101Ra\u2013treated group 0.7 \u00b1 0.3 mm, 4 mg rHuIL\u20101Ra\u2013treated group 0.5 \u00b1 0.3 mm) of femoral condyle osteophytes. In addition, a dose\u2010dependent decrease in the size (saline\u2010treated group 24.40 \u00b1 8.17 mm\n                    <jats:sup>2<\/jats:sup>\n                    , 2 mg rHuIL\u20101Ra\u2013treated group 20.90 \u00b1 8.01 mm\n                    <jats:sup>2<\/jats:sup>\n                    , 4 mg rHuIL\u20101Ra\u2013treated group 7.70 \u00b1 5.16 mm\n                    <jats:sup>2<\/jats:sup>\n                    ) and the grade (0\u20134 scale; saline\u2010treated group 1.20 \u00b1 0.29, 2 mg rHuIL\u20101Ra\u2013treated group 1.00 \u00b1 0.26, 4 mg rHuIL\u20101Ra\u2013treated group 0.30 \u00b1 0.21) of the tibial plateau cartilage lesions was found, with a significant difference (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.04) reached only with 4 mg rHuIL\u20101Ra. Similarly, the histologic lesions in dogs treated with 4 mg rHuIL\u20101Ra (Mankin scale; mean \u00b1 SEM 2.95 \u00b1 0.53) were significantly less severe (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.002) compared with those in the saline\u2010treated group (4.95 \u00b1 0.54). Importantly, rHuIL\u20101Ra treatment led to a significant reduction (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.005) of collagenase\u20101 expression in OA cartilage.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusion<\/jats:italic>\n                    . This study demonstrated that intraarticular injections of rHuIL\u20101Ra can protect against the development of experimentally induced OA lesions. This effect could result, at least in part, from a reduction of collagenase\u20101 expression. However, other catabolic processes involved in the degradation of OA cartilage may also be affected.\n                  <\/jats:p>","DOI":"10.1002\/art.1780390914","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T07:01:54Z","timestamp":1171436514000},"page":"1535-1544","source":"Crossref","is-referenced-by-count":318,"title":["Chondroprotective effect of intraarticular injections of interleukin\u20101 receptor antagonist in experimental osteoarthritis. Suppression of collagenase\u20101 expression"],"prefix":"10.1002","volume":"39","author":[{"given":"John P.","family":"Caron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio C.","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne","family":"Martel\u2010Pelletier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginette","family":"Tardif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Mineau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changshan","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"Pelletier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,12]]},"reference":[{"key":"e_1_2_1_2_2","volume-title":"Arthritis and Allied Conditions: A Textbook of Rheumatology","author":"Pelletier 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