{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:06:11Z","timestamp":1792098371966,"version":"4.4.0"},"reference-count":70,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,5,25]],"date-time":"2007-05-25T00:00:00Z","timestamp":1180051200000},"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":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To analyze genome\u2010wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham\u2010operated knees. Affymetrix GeneChip expression arrays were used to assess genome\u2010wide changes in gene expression. Expression patterns of selected dysregulated genes, including <jats:italic>Col2a1, Mmp13, Adamts5, Ctsc, Ptges<\/jats:italic>, and <jats:italic>Cxcr4<\/jats:italic>, were validated by real\u2010time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After normalization, comparison of OA and sham\u2010operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression \u22651.5\u2010fold, 722 with changes \u22652\u2010fold, 135 with changes \u22654\u2010fold, and 20 with changes of 8\u2010fold. Dysregulated genes known to be involved in human OA included <jats:italic>Mmp13, Adamts5<\/jats:italic>, and <jats:italic>Ptgs2<\/jats:italic>, among others. Several dysregulated genes (e.g., <jats:italic>Reln, Phex<\/jats:italic>, and <jats:italic>Ltbp2<\/jats:italic>) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including <jats:italic>Cxcr4<\/jats:italic> and <jats:italic>Ccl2<\/jats:italic>, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22711","type":"journal-article","created":{"date-parts":[[2007,5,28]],"date-time":"2007-05-28T07:47:56Z","timestamp":1180338476000},"page":"1854-1868","source":"Crossref","is-referenced-by-count":209,"title":["Global analyses of gene expression in early experimental osteoarthritis"],"prefix":"10.1002","volume":"56","author":[{"given":"C. T. G.","family":"Appleton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Pitelka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Beier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,5,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.023796"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11088"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-133-5-200009050-00007"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2006.01.020"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2006.01.006"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108676"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1880823"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.46.30576"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360906"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.90.1.78"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2002.005298"},{"key":"e_1_2_6_13_2","first-page":"236","article-title":"Differential expression of collagen types I, II, III, and X in human osteophytes","volume":"73","author":"Aigner T","year":"1995","journal-title":"Lab Invest"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(96)90150-X"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E05-01-0084"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22174"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21638"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2004.07.007"},{"key":"e_1_2_6_19_2","first-page":"221","article-title":"Animal models of osteoarthritis","volume":"39","author":"Brandt KD","year":"2002","journal-title":"Biorheology"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2000.0390"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2120"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200009)43:9<2121::AID-ANR24>3.0.CO;2-N"},{"key":"e_1_2_6_23_2","first-page":"504","article-title":"Evaluation of the rat stifle joint after transection of the cranial cruciate ligament and partial medial meniscectomy","volume":"51","author":"Karahan S","year":"2001","journal-title":"Comp Med"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20124"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.08.007"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2002.0823"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki456"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki500"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.09.027"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03369"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200431200"},{"key":"e_1_2_6_32_2","first-page":"603","article-title":"MMP\u20102\/gelatinase A is a gene product of human adult articular chondrocytes and is increased in osteoarthritic cartilage","volume":"22","author":"Duerr S","year":"2004","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119316"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10531"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118475"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510146200"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2002.0789"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.1998.0217"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050369"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11209"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-198163010-00017"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00624a009"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/267531a0"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1489"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.2.135"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-001-0064-8"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2005.01.003"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000143838.53434.b8"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500962200"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(00)00428-2"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20874"},{"key":"e_1_2_6_52_2","first-page":"345","article-title":"In\u2010vitro analysis of the expression of TGF\u03b2\u2010superfamily\u2010members during chondrogenic differentiation of mesenchymal stem cells and chondrocytes during dedifferentiation in cell culture","volume":"10","author":"Goessler UR","year":"2005","journal-title":"Cell Mol Biol Lett"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502249102"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/0470867639.ch10"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20615"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-7-30"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.bot.0000246468.80635.ef"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.06.002"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411793200"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2004.05.009"},{"key":"e_1_2_6_61_2","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1302\/0301-620X.55B3.588","article-title":"Chondrocyte multiplication in osteoarthritic articular cartilage","volume":"55","author":"Rothwell AG","year":"1973","journal-title":"J Bone Joint Surg Br"},{"key":"e_1_2_6_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1304::AID-ART222>3.0.CO;2-T"},{"key":"e_1_2_6_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(91)90274-7"},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(96)90114-6"},{"key":"e_1_2_6_65_2","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.86B2.14474"},{"key":"e_1_2_6_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21621"},{"key":"e_1_2_6_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200105)44:5<1056::AID-ANR186>3.0.CO;2-U"},{"key":"e_1_2_6_68_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115885"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11474"},{"key":"e_1_2_6_70_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.9.5781"},{"key":"e_1_2_6_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200108)44:8<1819::AID-ART319>3.0.CO;2-4"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.22711","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.22711","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T18:34:12Z","timestamp":1697049252000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.22711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5,25]]},"references-count":70,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2007,6]]}},"alternative-id":["10.1002\/art.22711"],"URL":"https:\/\/doi.org\/10.1002\/art.22711","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,25]]}}}