{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:37:12Z","timestamp":1780393032951,"version":"3.54.1"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,12,29]],"date-time":"2011-12-29T00:00:00Z","timestamp":1325116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the chondroprotective effect of cyclooxygenase 2 (COX\u20102) inhibition in experimental osteoarthritis (OA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of prostaglandin E<jats:sub>2<\/jats:sub>synthetic enzymes was examined by immunostaining of tibial cartilage from mice with surgically induced knee joint instability and from OA patients undergoing total knee arthroplasty. The effect of orally administered celecoxib (10 mg\/kg\/day and 30 mg\/kg\/day) or vehicle alone in mice was examined 12 weeks after the induction of OA. To investigate the involvement of COX\u20101 and COX\u20102 in OA development, we also created the model in COX\u20101\u2013homozygous\u2010knockout (<jats:italic>Ptgs1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice and COX\u20102\u2013homozygous\u2010knockout (<jats:italic>Ptgs2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice. OA severity was assessed using a grading system developed by our group and by the Osteoarthritis Research Society International scoring system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In mouse and human OA cartilage, the expression of the inducible enzymes COX\u20102 and microsomal prostaglandin E synthase 1 (mPGES\u20101) was enhanced, while that of the constitutive enzymes COX\u20101, cytosolic PGES, and mPGES\u20102 was suppressed. Daily celecoxib treatment did not prevent cartilage degradation or osteophyte formation during OA development in the mouse model. Furthermore, neither<jats:italic>Ptgs1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice nor<jats:italic>Ptgs2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice exhibited any significant difference in OA development as compared to wild\u2010type littermates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The two COX enzymes differ in terms of regulation of their expression during OA development. Nevertheless, experiments using inhibitor and genetic deficiency demonstrated a lack of chondroprotective effect of COX\u20102 inhibition in the mouse surgical OA model.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.33324","type":"journal-article","created":{"date-parts":[[2011,9,8]],"date-time":"2011-09-08T19:58:52Z","timestamp":1315511932000},"page":"198-203","source":"Crossref","is-referenced-by-count":38,"title":["Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice"],"prefix":"10.1002","volume":"64","author":[{"given":"Atsushi","family":"Fukai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kamekura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daichi","family":"Chikazu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Hosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kozo","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ung\u2010il","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,29]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10356"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(03)00037-7"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015504632021"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.04.006"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1846"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.09.002"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kei187"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1063-4584(10)60355-X"},{"key":"e_1_2_7_10_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1016-8478(23)17544-3","article-title":"Endochondral ossification signals in cartilage degradation during osteoarthritis progression in experimental mouse models","volume":"25","author":"Kawaguchi H","year":"2008","journal-title":"Mol Cells"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23683"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/378406a0"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.03.004"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.07.014"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23158"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/38.8.714"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004543"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215681"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.030"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.04.015"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.05.001"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2010.11.003"}],"container-title":["Arthritis &amp; 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