{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:16:01Z","timestamp":1790162161355,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,9,18]],"date-time":"2006-09-18T00:00:00Z","timestamp":1158537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bacterial arthritis is a progressive joint disease which includes rapid destruction of articular cartilage even after clearance of the causal factor. The resulting post\u2010infectious arthropathy is mainly characterized by self\u2010perpetuating joint destruction and extensive angiogenesis in the emerging pannus\u2010like synovial membrane, but the underlying molecular mechanisms of the bacteria\u2010initiated process remain incompletely understood. This study was conducted to elucidate the expression and regulation of angiogenic and cartilage\u2010destructive vascular endothelial growth factor (VEGF) in septic arthritis. For that purpose, aspirates of synovial fluid from patients with pyogenic arthritis were examined for VEGF levels by ELISA. <jats:italic>In vitro<\/jats:italic> studies with primary and immortalized chondrocytes were performed to determine whether Gram\u2010positive and Gram\u2010negative bacteria induce VEGF expression, by using real\u2010time RT\u2010PCR, ELISA, and immunohistochemistry. Activation of the transcription factor AP\u20101 was assessed by EMSA experiments. The necessity of the Toll\u2010like receptor\u20102 (TLR\u20102), ERK\u20101\/\u20102, and AP\u20101 pathway for infectious VEGF induction in chondrocytes was examined by using specific blocking reagents. ELISA experiments revealed that aspirates of synovial fluid from patients with pyogenic arthritis contain elevated levels of VEGF. The <jats:italic>in vitro<\/jats:italic> results confirmed the transcriptional induction of VEGF in chondrocytes after bacterial challenge by real\u2010time RT\u2010PCR, ELISA, and immunohistochemistry. This activation was mediated by a TLR\u20102\u2010, ERK\u20101\/\u20102\u2010, and AP\u20101\u2010dependent pathway. The findings demonstrate the expression of Toll\u2010like receptors on mesenchymal articular chondrocytes and reveal TLR\u20102\u2010mediated VEGF induction in human chondrocytes after Gram\u2010positive bacterial sensing. Since VEGF is a potent angiogenic and tissue remodelling factor, evidence that Toll\u2010like receptors contribute to destructive arthropathy after microbial joint infection is provided. VEGF may be a therapeutic target in the future for the prevention of post\u2010infectious cartilage degradation in articular joints. Copyright \u00a9 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2059","type":"journal-article","created":{"date-parts":[[2006,9,18]],"date-time":"2006-09-18T08:26:11Z","timestamp":1158567971000},"page":"315-324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["TLR\u20102\u2010mediated induction of vascular endothelial growth factor (VEGF) in cartilage in septic joint disease"],"prefix":"10.1002","volume":"210","author":[{"given":"D","family":"Varoga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Paulsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Mentlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Fay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Kurz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Sch\u00fctz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Wruck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MB","family":"Goldring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Pufe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,9,18]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)09522-6"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(97)80540-0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/9554"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200010)43:10<2283::AID-ANR16>3.0.CO;2-9"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111166"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198503213121206"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001099900019"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.1.9"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5929"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.5.853"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.2.603"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63109-4"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63491-8"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0055fje"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200105)44:5<1082::AID-ANR188>3.0.CO;2-X"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.60.11.1070"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63808-4"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1527"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.4.450"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200107040"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1116"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1398-9995.2003.00225.x"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141126"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117595"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.1999.0277"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020928"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.2.289"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301676200"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10942"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1142"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.3109\/08977199809017488"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.7.2488.2488"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/9467"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197412192912507"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.9.4853"},{"key":"e_1_2_6_38_2","first-page":"1624","article-title":"Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis","volume":"22","author":"Nagashima M","year":"1995","journal-title":"J Rheumatol"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.6.3503-3511.2003"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20437"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2004.06.003"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2059","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:20:17Z","timestamp":1761052817000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,18]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,11]]}},"alternative-id":["10.1002\/path.2059"],"URL":"https:\/\/doi.org\/10.1002\/path.2059","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,18]]},"assertion":[{"value":"2006-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}