{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:51:25Z","timestamp":1789390285088,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T00:00:00Z","timestamp":1437609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Accumulating evidence points to the importance of the innate immune system in inflammation\u2010induced bone loss in infectious and autoimmune diseases. TLRs are well known for being activated by ligands expressed by bacteria, viruses, and fungi. Recent findings indicate that also endogenous ligands in inflammatory processes are important, one being a TLR5 agonist present in synovial fluid from patients with rheumatoid arthritis (RA). We found that activation of TLR5 by its specific ligand, flagellin, caused robust osteoclast formation and bone loss in cultured mouse neonatal parietal bones dependent on increased receptor activator of NF\u2010\u03baB ligand (RANKL):osteoprotegerin ratio, with half\u2010maximal stimulation at 0.01 \u03bcg\/ml. Flagellin enhanced\n                    <jats:italic>Rankl<\/jats:italic>\n                    mRNA in isolated osteoblasts by a myeloid differentiation primary response gene 88 and NF\u2010\u03baB\u2010dependent mechanism. Injection of flagellin locally over skull bones in 5\u2010wk\u2010old mice resulted in increased mRNA expression of\n                    <jats:italic>Rankl<\/jats:italic>\n                    and osteoclastic genes, robust osteoclast formation, and bone loss. The effects\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    were absent in\n                    <jats:italic>Tlr5<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice. These data show that TLR5 is a novel activator of RANKL and osteoclast formation and, therefore, a potential key factor in inflammation\u2010induced bone erosions in diseases like RA, reactive arthritis, and periodontitis. TLR5 might be a promising novel treatment target for prevention of inflammatory bone loss.\u2014Kassem, A., Henning, P., Kindlund, B., Lindholm, C., Lerner, U. H. TLR5, a novel mediator of innate immunity\u2010induced osteoclastogenesis and bone loss.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    29, 4449\u20104460 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.15-272559","type":"journal-article","created":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T22:30:34Z","timestamp":1437690634000},"page":"4449-4460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["TLR5, a novel mediator of innate immunity\u2010induced osteoclastogenesis and bone loss"],"prefix":"10.1096","volume":"29","author":[{"given":"Ali","family":"Kassem","sequence":"first","affiliation":[{"name":"Department of Molecular Periodontology Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Henning","sequence":"additional","affiliation":[{"name":"Centre for Bone and Arthritis Research Department of Internal Medicine and Clinical Nutrition Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Kindlund","sequence":"additional","affiliation":[{"name":"Centre for Bone and Arthritis Research Department of Internal Medicine and Clinical Nutrition Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Lindholm","sequence":"additional","affiliation":[{"name":"Centre for Bone and Arthritis Research Department of Internal Medicine and Clinical Nutrition Gothenburg Sweden"},{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf H.","family":"Lerner","sequence":"additional","affiliation":[{"name":"Department of Molecular Periodontology Ume\u00e5 University Ume\u00e5 Sweden"},{"name":"Centre for Bone and Arthritis Research Department of Internal Medicine and Clinical Nutrition Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00511"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820139.2013.822766"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2010.43.8.513"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.167"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.153"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930701694469"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30290"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-178301"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.06.007"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2010.529976"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1253"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.7.3688"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2007.00410.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28898"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103217200"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22398"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0802"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/35074106"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.09.002"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:33:1:083"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102977"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37992"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.9.516"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.12.7183-7189.2004"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2008.00448.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2008.00473.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202511"},{"key":"e_1_2_7_30_1","first-page":"3092","article-title":"Ligation of TLR5 promotes myeloid cell infiltration and differentiation into mature osteoclasts in rheumatoid arthritis and experimental arthritis","volume":"193","author":"Kim S. 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