{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:36:01Z","timestamp":1790807761198,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T00:00:00Z","timestamp":1382918400000},"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":[[2013,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The protease HTRA\u20101 is closely associated with rheumatoid arthritis (RA). The molecular mechanisms that control HTRA\u20101 expression are currently unknown. This study was undertaken to determine the regulatory role of Toll\u2010like receptors (TLRs) on HTRA\u20101 expression in mice with collagen\u2010induced arthritis (CIA) and in synovial cells from RA patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HTRA\u20101 messenger RNA and protein production in mouse fibroblasts, mouse macrophages, and freshly isolated RA patient synovial cells treated with TLR ligands were detected by real\u2010time polymerase chain reaction and enzyme\u2010linked immunosorbent assay, respectively. Arthritis incidence and severity were determined using clinical scores and histopathologic analysis. Involvement of HTRA\u20101 in lipopolysaccharide (LPS)\u2013increased arthritis incidence and severity in mice was determined using anti\u2013HTRA\u20101 monoclonal antibody. The signal pathways involved in HTRA\u20101 expression were accessed by specific inhibitors, RNA interference, dual\u2010luciferase reporter, and chromatin immunoprecipitation methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LPS and tenascin\u2010C, but not the other TLR ligands tested, strongly induced HTRA\u20101 expression. LPS significantly increased HTRA\u20101 expression in the joint tissue as well as arthritis incidence and severity in mice with CIA. Blocking HTRA\u20101 by antibody significantly decreased LPS\u2010promoted CIA severity. Inhibiting NF\u2010\u03baB significantly decreased LPS\u2010induced HTRA\u20101 expression in mouse and human cells. Dual\u2010luciferase reporter assay and ChIP analysis showed that p65 directly binds to HTRA\u20101 promoter (amino acid 347).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that TLR\u20104 activation increases HTRA\u20101 expression through the NF\u2010\u03baB pathway in fibroblasts and macrophages. HTRA\u20101 expression is involved in the enhancing effects of LPS on CIA. This study offers new insights into the regulation of HTRA\u20101 expression via LPS\/TLR\u20104 and the role of HTRA\u20101 in RA pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.38124","type":"journal-article","created":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T16:46:59Z","timestamp":1377622019000},"page":"2835-2846","source":"Crossref","is-referenced-by-count":43,"title":["Lipopolysaccharide Increases the Incidence of Collagen\u2010Induced Arthritis in Mice Through Induction of Protease HTRA\u20101 Expression"],"prefix":"10.1002","volume":"65","author":[{"given":"Yuzhu","family":"Hou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, and Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijiang","family":"Lin","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch Galveston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linnan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, and Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoting","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, and Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanlei","family":"Hu","sequence":"additional","affiliation":[{"name":"Clinical Immunology Center and Peking University People's Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, and Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, and Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, and General Hospital of Chinese People's Armed Police Forces Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard F.","family":"Godley","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch Galveston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, and Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanguo","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Immunology Center and Peking University People's Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, and Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36389"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0b013e3180690616"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/17402520600576578"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24127"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32639"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.7021"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060657"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-009-0051-z"},{"key":"e_1_2_7_10_1","first-page":"1439","article-title":"Tenascin and fibronectin distribution in human normal and pathological synovium","volume":"19","author":"Cutolo M","year":"1992","journal-title":"J Rheumatol"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1987"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00658-5"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.03.015"},{"key":"e_1_2_7_14_1","first-page":"599","article-title":"Role of HTRA1, a serine protease, in the progression of articular cartilage degeneration","volume":"25","author":"Polur I","year":"2010","journal-title":"Histol Histopathol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.114"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022959"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4853"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(96)01229-X"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.275990"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.51.34406"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500361200"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22876"},{"key":"e_1_2_7_23_1","first-page":"1274","article-title":"Association of the HTRA1 \u2010625G>A promoter gene polymorphism with exudative age\u2010related macular degeneration in a Central European population","volume":"13","author":"Weger M","year":"2007","journal-title":"Mol Vis"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-3069"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1102853108"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(02)00093-7"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040435"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27698"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0304-8"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22891"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23063"},{"key":"e_1_2_7_32_1","first-page":"207","article-title":"Collagen\u2010induced arthritis as a model for rheumatoid arthritis","volume":"98","author":"Williams RO","year":"2004","journal-title":"Methods Mol Med"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(03)00528-5"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-09-0473"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.02.025"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.08.014"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.158"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118748109"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.17224711"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.3105cm1"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38124","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T02:08:34Z","timestamp":1698631714000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.38124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,28]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1002\/art.38124"],"URL":"https:\/\/doi.org\/10.1002\/art.38124","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718087873.793485112","asserted-by":"object"}]},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,28]]}}}