{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T18:44:48Z","timestamp":1785005088292,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T00:00:00Z","timestamp":1369872000000},"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":[[2013,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify changes in gene expression in mice with osteoarthritis (OA) in order to explore the mechanisms of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene expression profiling was performed in cartilage from mice with surgically induced OA. We used wild\u2010type (WT) mice and <jats:italic>Adamts5<\/jats:italic>\u0394cat mice, in which ADAMTS\u20105 activity is lacking and aggrecan loss and cartilage erosion are inhibited, to distinguish gene expression changes that are independent of ADAMTS\u20105 activity and cartilage breakdown. Mechanical instability was introduced into the knee joints of 10\u2010week\u2010old male mice via surgical destabilization of the medial meniscus (DMM). Cartilage from the developing lesion in the destabilized medial meniscus and corresponding regions in sham\u2010operated joints was harvested by microdissection at 1, 2, and 6 weeks postsurgery, and RNA was extracted, amplified, and hybridized to whole\u2010genome microarrays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Several previously identified OA\u2010related genes, including <jats:italic>Ptgs2, Crlf1,<\/jats:italic> and <jats:italic>Inhba<\/jats:italic>, and novel genes, such as <jats:italic>Phdla2<\/jats:italic> and <jats:italic>Il11,<\/jats:italic> were up\u2010regulated in both WT mice and <jats:italic>Adamts5<\/jats:italic>\u0394cat mice, indicating that they are independent of ADAMTS\u20105 activity. The altered expression of other genes, including <jats:italic>Col10a1<\/jats:italic>, the sentinel marker of cartilage hypertrophy, and Wnt\/\u03b2\u2010catenin pathway genes, required ADAMTS\u20105 activity. Cell death pathway genes were dysregulated, and Tp53, Foxo4, and Xbp1 endoplasmic reticulum\u2013stress transcriptional networks were activated. Analysis of degradome genes identified up\u2010regulation of many proteases, including <jats:italic>Mmp3<\/jats:italic>, <jats:italic>Capn2,<\/jats:italic> and the novel cartilage proteases <jats:italic>Prss46<\/jats:italic> and <jats:italic>Klk8<\/jats:italic>. Comparison with other studies identified 16 genes also dysregulated in rat and human OA as priorities for study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We have identified, for the first time, several genes that have an ADAMTS\u20105\u2013independent role in OA, identifying them as possible OA initiation candidates. This work provides new insights into the sequence of gene dysregulation and the molecular basis of cartilage destruction in OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37900","type":"journal-article","created":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T21:10:44Z","timestamp":1361567444000},"page":"1547-1560","source":"Crossref","is-referenced-by-count":66,"title":["Transcriptomics of Wild\u2010Type Mice and Mice Lacking ADAMTS\u20105 Activity Identifies Genes Involved in Osteoarthritis Initiation and Cartilage Destruction"],"prefix":"10.1002","volume":"65","author":[{"given":"John F.","family":"Bateman","sequence":"first","affiliation":[{"name":"Murdoch Childrens Research Institute and University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Rowley","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute Parkville Victoria 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