{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T10:44:01Z","timestamp":1784371441768,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["RR027553"],"award-info":[{"award-number":["RR027553"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["R21DE023178"],"award-info":[{"award-number":["R21DE023178"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE024796"],"award-info":[{"award-number":["R01DE024796"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Apical periodontitis (periapical lesions) is an infection\u2010induced chronic inflammation in the jaw, ultimately resulting in the destruction of apical periodontal tissue. Toll\u2010like receptors (TLRs) are prominent in the initial recognition of pathogens. Our previous study showed that TLR4 signaling is proinflammatory in periapical lesions induced by a polymicrobial endodontic infection. In contrast, the functional role of TLR2 in regulation of periapical tissue destruction is still not fully understood. Using TLR2 deficient (KO), TLR2\/TLR4 double deficient (dKO), and wild\u2010type (WT) mice, we demonstrate that TLR2 KO mice are highly responsive to polymicrobial infection\u2010induced periapical lesion caused by over activation of TLR4 signal transduction pathway that resulted in elevation of NF\u2010kB (nuclear factor kappa B) and proinflammatory cytokine production. The altered TLR4 signaling is caused by TLR2 deficiency\u2010dependent elevation of CD14 (cluster of differentiation 14), which is a co\u2010receptor of TLR4. Indeed, neutralization of CD14 strikingly suppresses TLR2 deficiency\u2010dependent inflammation and tissue destruction <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Our findings suggest that a network of TLR2, TLR4, and CD14 is a key factor in regulation of polymicrobial dentoalveolar infection and subsequent tissue destruction. Anat Rec, 299:1281\u20131292, 2016. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ar.23383","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T19:14:59Z","timestamp":1466190899000},"page":"1281-1292","source":"Crossref","is-referenced-by-count":22,"title":["Elevated CD14 (Cluster of Differentiation 14) and Toll\u2010Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice"],"prefix":"10.1002","volume":"299","author":[{"given":"Daniel","family":"Rider","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases the Forsyth Institute Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisako","family":"Furusho","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Pathobiology Hiroshima University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases the Forsyth Institute Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Trachtenberg","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology Harvard School of Dental Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winston Patrick","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology Harvard School of Dental Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimito","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases the Forsyth Institute Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Susa","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Endodontology Graduate School of Dentistry, Tohoku University Sendai Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Bahammam","sequence":"additional","affiliation":[{"name":"Department of Endodontics Faculty of Dentistry, King Abdulaziz University  Jeddah 21589 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Stashenko","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases the Forsyth Institute Cambridge Massachusetts"},{"name":"Department of Oral Medicine Infection, and Immunity, Harvard School of Dental Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Fujimura","sequence":"additional","affiliation":[{"name":"Division of Functional Morphology Department of Anatomy Iwate Medical University Morioka Iwate 020\u20108505 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases the Forsyth Institute Cambridge Massachusetts"},{"name":"Department of Oral Medicine Infection, and Immunity, Harvard School of Dental Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.07.001"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202194"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)62925-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8296"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-0266(03)00156-6"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2012.03.017"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2337"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.DON.0000133157.60731.3F"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1671"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0512220"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2006.12.003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306906101"},{"key":"e_1_2_6_14_1","first-page":"291","article-title":"Sequential morphological and quantitative changes in blood and bone marrow neutrophils in dogs with acute inflammation","volume":"49","author":"Gossett KA","year":"1985","journal-title":"Can J Comp Med"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2918"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.7.3749"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.10.5645-5651.2000"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4681-4687.2000"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.7.3541"},{"key":"e_1_2_6_20_1","first-page":"79","article-title":"Structure\u2010function analysis of soluble and membrane\u2010bound CD14","volume":"397","author":"Kirkland TN","year":"1998","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3132"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.060224"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1542\/peds.74.5.823","article-title":"Degenerative changes in neutrophils: an indicator of bacterial infection","volume":"74","author":"Liu CH","year":"1984","journal-title":"Pediatrics"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1979.03630430051016"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/35100529"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205966200"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2001.02385.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202511"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050654"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.11.1.106-110.2004"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.7.3626"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.10.5392"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80119-3"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.1995.tb00145.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2038"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301783"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.1993.tb00543.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.7.4463"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09421"}],"container-title":["The Anatomical Record"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Far.23383","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.23383","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:27:20Z","timestamp":1759951640000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/ar.23383"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,6]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1002\/ar.23383"],"URL":"https:\/\/doi.org\/10.1002\/ar.23383","archive":["Portico"],"relation":{},"ISSN":["1932-8486","1932-8494"],"issn-type":[{"value":"1932-8486","type":"print"},{"value":"1932-8494","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,6]]}}}