{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:10:56Z","timestamp":1790727056072,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:00:00Z","timestamp":1372723200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine the ability of a broad\u2010spectrum histone deacetylase (HDAC) inhibitor to protect cartilage in vivo, and to explore the effects of class\u2010selective HDAC inhibitors and small interfering RNA (siRNA)\u2013induced knockdown of HDACs on metalloproteinase expression and cartilage degradation in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A destabilization of the medial meniscus (DMM) model was used to assess the in vivo activity of the HDAC inhibitor trichostatin A (TSA). Human articular chondrocytes (HACs) and SW\u20101353 chondrosarcoma cells were treated with cytokines and TSA, valproic acid, MS\u2010275, or siRNA, and quantitative reverse transcription\u2013polymerase chain reaction was performed to determine the effect of treatment on metalloproteinase expression. HDAC inhibitor activity was detected by Western blotting. A bovine nasal cartilage (BNC) explant assay was performed to measure cartilage resorption in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Systemically administered TSA protected cartilage in the DMM model. TSA, valproic acid, and MS\u2010275 repressed cytokine\u2010induced\n                      <jats:italic>MMP1<\/jats:italic>\n                      and\n                      <jats:italic>MMP13<\/jats:italic>\n                      expression in HACs. Knockdown of each class I HDAC diminished interleukin\u20101\u2013induced\n                      <jats:italic>MMP13<\/jats:italic>\n                      expression. All of the HDAC inhibitors prevented degradation of BNC, in which TSA and MS\u2010275 repressed cytokine\u2010induced\n                      <jats:italic>MMP<\/jats:italic>\n                      expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inhibition of class I HDACs (HDAC\u20101, HDAC\u20102, HDAC\u20103) by MS\u2010275 or by specific depletion of HDACs is capable of repressing cytokine\u2010induced metalloproteinase expression in cartilage cells and BNC explants, resulting in inhibition of cartilage resorption. These observations indicate that specific inhibition of class I HDACs is a possible therapeutic strategy in the arthritides.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.37965","type":"journal-article","created":{"date-parts":[[2013,4,10]],"date-time":"2013-04-10T15:18:37Z","timestamp":1365607117000},"page":"1822-1830","source":"Crossref","is-referenced-by-count":78,"title":["Class I Histone Deacetylase Inhibition Modulates Metalloproteinase Expression and Blocks Cytokine\u2010Induced Cartilage Degradation"],"prefix":"10.1002","volume":"65","author":[{"given":"Kirsty L.","family":"Culley","sequence":"first","affiliation":[{"name":"University of East Anglia Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Hui","sequence":"additional","affiliation":[{"name":"Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt J.","family":"Barter","sequence":"additional","affiliation":[{"name":"Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose K.","family":"Davidson","sequence":"additional","affiliation":[{"name":"University of East Anglia Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey E.","family":"Swingler","sequence":"additional","affiliation":[{"name":"University of East Anglia Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auriane P. M.","family":"Destrument","sequence":"additional","affiliation":[{"name":"Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny L.","family":"Scott","sequence":"additional","affiliation":[{"name":"Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon T.","family":"Donell","sequence":"additional","affiliation":[{"name":"Norfolk and Norwich University Hospital Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Fenwick","sequence":"additional","affiliation":[{"name":"Smith &amp; Nephew Heslington York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Rowan","sequence":"additional","affiliation":[{"name":"Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Young","sequence":"additional","affiliation":[{"name":"Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Clark","sequence":"additional","affiliation":[{"name":"University of East Anglia Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2592"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175371"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1702"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-010-0055-9"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00235-1"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00058"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707165"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.10.014"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20709"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2741\/2079"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1693"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.16.7.1111"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2689"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.6969"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-0799"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.02.009"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306752200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4563"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404603101"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071728"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11433"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.079574"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-299-5_20"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac60205a053"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2013"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-011-9508-8"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/417455a"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.160"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-009-0224-7"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-133215"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502409200"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700599200"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/08977190802625179"}],"container-title":["Arthritis &amp; 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