{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:57:57Z","timestamp":1791262677432,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T00:00:00Z","timestamp":1151280000000},"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":[[2006,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine the catabolic pathways mediated by Toll\u2010like receptor (TLR) ligands in human osteoarthritic (OA) chondrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The presence of TLRs in OA and non\u2010OA articular cartilage was analyzed by immunohistochemistry. The regulation of TLR messenger RNA (mRNA) by interleukin\u20101 (IL\u20101) and tumor necrosis factor \u03b1 (TNF\u03b1) was analyzed by reverse transcription\u2013polymerase chain reaction. For stimulation of TLR\u20102 and TLR\u20104, chondrocytes were treated with\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      peptidoglycan and lipopolysaccharides (LPS), respectively. Production of matrix metalloproteinases (MMPs) 1, 3, and 13 and prostaglandin E\n                      <jats:sub>2<\/jats:sub>\n                      (PGE\n                      <jats:sub>2<\/jats:sub>\n                      ) was evaluated by enzyme\u2010linked immunosorbent assay. Production of nitric oxide (NO) was analyzed by the Griess reaction. Regulation of cyclooxygenase 2 protein and phosphorylation of MAPKs (p38, ERK, and JNK) were evaluated by Western blotting or solid\u2010phase kinase assay. NF\u2010\u03baB activation was evaluated by electrophoretic mobility shift assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Expression of TLRs 2 and 4 was up\u2010regulated in lesional areas of OA cartilage. Treatment with IL\u20101, TNF\u03b1, peptidoglycan, and LPS all significantly up\u2010regulated TLR\u20102 mRNA expression in cultured chondrocytes. Production of MMPs 1, 3, and 13 and of NO and PGE\n                      <jats:sub>2<\/jats:sub>\n                      was significantly increased after treating chondrocytes with either of the TLR ligands. Prolonged culture of cartilage explants with TLR ligands also led to a significant increase in the release of proteoglycan and type II collagen degradation product. Treatment with TLR ligands led to phosphorylation of all 3 MAPKs and activation of NF\u2010\u03baB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We found that TLRs are increased in OA cartilage lesions. TLR\u20102 and TLR\u20104 ligands strongly induce catabolic responses in chondrocytes. Modulation of TLR\u2010mediated signaling as a therapeutic strategy would require detailed elucidation of the signaling pathways involved.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.21951","type":"journal-article","created":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T19:06:55Z","timestamp":1151348815000},"page":"2152-2163","source":"Crossref","is-referenced-by-count":251,"title":["The catabolic pathway mediated by Toll\u2010like receptors in human osteoarthritic chondrocytes"],"prefix":"10.1002","volume":"54","author":[{"given":"Hyun Ah","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u2010La","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Young","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Sik","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Yeon","family":"Jhun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hey Jwa","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho\u2010Youn","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,6,27]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.2741\/1817"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1003"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021955"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00994-5"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3240305"},{"key":"e_1_2_5_7_2","first-page":"75","article-title":"Chondrocyte apoptosis induced by nitric oxide","volume":"146","author":"Blanco FJ","year":"1995","journal-title":"Am J Pathol"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)01004-3"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20632"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35100529"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.083001.084359"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.10.005"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.4.508"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63918-1"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10848"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.2.1256"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6145"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.04.017"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.8.5016"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.15.6419"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11014"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200003)43:3<593::AID-ANR16>3.0.CO;2-1"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.5736"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20678"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21278"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01627.x"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-5-2"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00831"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00082.2003"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041817"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308620200"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21155"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21214"}],"container-title":["Arthritis &amp; 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