{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T21:46:32Z","timestamp":1780091192336,"version":"3.54.0"},"reference-count":50,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1016\/j.jbc.2022.101603","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T19:08:48Z","timestamp":1643483328000},"page":"101603","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Endosomal TLR3 signaling in stromal osteoblasts induces prostaglandin E2\u2013mediated inflammatory periodontal bone resorption"],"prefix":"10.1016","volume":"298","author":[{"given":"Tsukasa","family":"Tominari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-8706","authenticated-orcid":false,"given":"Miyuki","family":"Akita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiho","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shosei","family":"Yoshinouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Karouji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshifumi","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Miyaura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Numabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Inada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2022.101603_bib1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1600-0757.2006.00170.x","article-title":"The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease","volume":"43","author":"Noguchi","year":"2007","journal-title":"Periodontol. 2000"},{"key":"10.1016\/j.jbc.2022.101603_bib2","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.4049\/jimmunol.177.3.1879","article-title":"Membrane-bound prostaglandin E synthase-1-mediated prostaglandin E2 production by osteoblast plays a critical role in lipopolysaccharide-induced bone loss associated with inflammation","volume":"177","author":"Inada","year":"2006","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib3","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1084\/jem.20030015","article-title":"An essential role of cytosolic phospholipase A2\u03b1 in prostaglandin E2\u2013mediated bone resorption associated with inflammation","volume":"197","author":"Miyaura","year":"2003","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.jbc.2022.101603_bib4","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.4049\/jimmunol.172.4.2504","article-title":"Suppression of osteoprotegerin expression by prostaglandin E2 is crucially involved in lipopolysaccharide-induced osteoclast formation","volume":"172","author":"Suda","year":"2004","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib5","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.lfs.2004.10.079","article-title":"IL-1\u03b1 stimulates the formation of osteoclast-like cells by increasing M-CSF and PGE2 production and decreasing OPG production by osteoblasts","volume":"77","author":"Tanabe","year":"2005","journal-title":"Life Sci."},{"key":"10.1016\/j.jbc.2022.101603_bib6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2022.101603_bib7","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1073\/pnas.95.7.3597","article-title":"Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL","volume":"95","author":"Yasuda","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2022.101603_bib8","first-page":"1","article-title":"Rankl: A therapeutic target for bone destruction in rheumatoid arthritis","volume":"28","author":"Tanaka","year":"2017","journal-title":"Mod. Rheumatol."},{"key":"10.1016\/j.jbc.2022.101603_bib9","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S1098-8823(03)00049-2","article-title":"Effects of selective prostaglandin EP2 and EP4 receptor agonists on bone resorption and formation in fetal rat organ cultures","volume":"71","author":"Raisz","year":"2003","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"10.1016\/j.jbc.2022.101603_bib10","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1210\/endo.141.4.7405","article-title":"The role of prostaglandin E receptor subtypes (EP1, EP2, EP3, and EP4) in bone resorption: An analysis using specific agonists for the respective EPs","volume":"141","author":"Suzawa","year":"2000","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2022.101603_bib11","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S8756-3282(02)00683-X","article-title":"Effects of prostaglandin E2 on gene expression in primary osteoblastic cells from prostaglandin receptor knockout mice","volume":"30","author":"Li","year":"2002","journal-title":"Bone"},{"key":"10.1016\/j.jbc.2022.101603_bib12","doi-asserted-by":"crossref","first-page":"19819","DOI":"10.1074\/jbc.M002079200","article-title":"Impaired bone resorption to prostaglandin E2in prostaglandin E receptor EP4-knockout mice","volume":"275","author":"Miyaura","year":"2000","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2022.101603_bib13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/164_2019_332","article-title":"Prostaglandins and bone","volume":"262","author":"Pilbeam","year":"2019","journal-title":"Handb. Exp. Pharmacol."},{"key":"10.1016\/j.jbc.2022.101603_bib14","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/jcp.24790","article-title":"The cooperation of CREB and NFAT is required for PTHrP-induced RANKL expression in mouse osteoblastic cells","volume":"230","author":"Park","year":"2015","journal-title":"J.\u00a0Cell Physiol."},{"key":"10.1016\/j.jbc.2022.101603_bib15","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.immuni.2011.05.006","article-title":"Toll-like receptors and their crosstalk with other innate receptors in infection and immunity","volume":"34","author":"Kawai","year":"2011","journal-title":"Immunity"},{"key":"10.1016\/j.jbc.2022.101603_bib16","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1902\/jop.2010.100004","article-title":"Gram-negative periodontal bacteria induce the activation of toll-like receptors 2 and 4, and cytokine production in human periodontal ligament cells","volume":"81","author":"Sun","year":"2010","journal-title":"J.\u00a0Periodontol."},{"key":"10.1016\/j.jbc.2022.101603_bib17","first-page":"2341","article-title":"LPS-induced upregulation of the TLR4 signaling pathway inhibits osteogenic differentiation of human periodontal ligament stem cells under inflammatory conditions","volume":"43","author":"Yu","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.jbc.2022.101603_bib18","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.bbrc.2012.10.016","article-title":"Toll-like receptor 2 heterodimers, TLR2\/6 and TLR2\/1 induce prostaglandin E production by osteoblasts, osteoclast formation and inflammatory periodontitis","volume":"428","author":"Matsumoto","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.jbc.2022.101603_bib19","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1399-302X.2008.00448.x","article-title":"Immunohistochemical localization of Toll-like receptors 1-10 in periodontitis","volume":"23","author":"Beklen","year":"2008","journal-title":"Oral Microbiol. Immun."},{"key":"10.1016\/j.jbc.2022.101603_bib20","first-page":"e48","article-title":"Increased nucleic acid receptor expression in chronic periodontitis","volume":"84","author":"Sahingur","year":"2013","journal-title":"J.\u00a0Periodontol."},{"key":"10.1016\/j.jbc.2022.101603_bib21","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1096\/fj.15-272559","article-title":"TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss","volume":"29","author":"Kassem","year":"2015","journal-title":"FASEB J."},{"key":"10.1016\/j.jbc.2022.101603_bib22","doi-asserted-by":"crossref","first-page":"12542","DOI":"10.1074\/jbc.M310175200","article-title":"mRNA is an endogenous ligand for Toll-like receptor 3","volume":"279","author":"Karik\u00f3","year":"2004","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2022.101603_bib23","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/nm.2861","article-title":"Ultraviolet radiation damages self noncoding RNA and is detected by TLR3","volume":"18","author":"Bernard","year":"2012","journal-title":"Nat. Med."},{"key":"10.1016\/j.jbc.2022.101603_bib24","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.immuni.2013.02.024","article-title":"Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-\u03b2","volume":"38","author":"Kawashima","year":"2013","journal-title":"Immunity"},{"key":"10.1016\/j.jbc.2022.101603_bib25","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.cellsig.2014.01.015","article-title":"TLR3 regulates mycobacterial RNA-induced IL-10 production through the PI3K\/AKT signaling pathway","volume":"26","author":"Bai","year":"2014","journal-title":"Cell Signal."},{"key":"10.1016\/j.jbc.2022.101603_bib26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fimmu.2017.00028","article-title":"TLR7 and TLR3 sense Brucella abortus RNA to induce proinflammatory cytokine production but they are dispensable for host control of infection","volume":"8","author":"Campos","year":"2017","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib27","doi-asserted-by":"crossref","first-page":"5656","DOI":"10.4049\/jimmunol.172.9.5656","article-title":"Arthritogenic properties of double-stranded (viral) RNA","volume":"172","author":"Zare","year":"2004","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.imlet.2009.02.006","article-title":"TLR-3 enhances osteoclastogenesis through upregulation of RANKL expression from fibroblast-like synoviocytes in patients with rheumatoid arthritis","volume":"124","author":"Kim","year":"2009","journal-title":"Immunol. Lett."},{"key":"10.1016\/j.jbc.2022.101603_bib29","doi-asserted-by":"crossref","first-page":"115","DOI":"10.4049\/jimmunol.1202136","article-title":"CD11b\/CD18 (Mac-1) is a novel surface receptor for extracellular double-stranded RNA to mediate cellular inflammatory responses","volume":"190","author":"Zhou","year":"2013","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib30","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1128\/IAI.66.9.4158-4162.1998","article-title":"Bone resorption caused by three periodontal pathogens in\u00a0vivo in mice is mediated in part by prostaglandin","volume":"66","author":"Zubery","year":"1998","journal-title":"Infect. Immun."},{"key":"10.1016\/j.jbc.2022.101603_bib31","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.4049\/jimmunol.162.7.3749","article-title":"Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: Evidence for TLR4 as the Lps gene product","volume":"162","author":"Hoshino","year":"1999","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib32","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1128\/IAI.02084-14","article-title":"Porphyromonas gingivalis exacerbates ligature-induced, RANKL-dependent alveolar bone resorption via differential regulation of toll-like receptor 2 (TLR2) and TLR4","volume":"82","author":"Lin","year":"2014","journal-title":"Infect. Immun."},{"key":"10.1016\/j.jbc.2022.101603_bib33","doi-asserted-by":"crossref","first-page":"24159","DOI":"10.1074\/jbc.M110.198085","article-title":"TLR2-dependent modulation of osteoclastogenesis by Porphyromonas gingivalis through differential induction of NFATc1 and NF-kappaB","volume":"286","author":"Zhang","year":"2011","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2022.101603_bib34","doi-asserted-by":"crossref","first-page":"501","DOI":"10.4049\/jimmunol.1100683","article-title":"TLR2 signaling and Th2 responses drive Tannerella forsythia-induced periodontal bone loss","volume":"187","author":"Myneni","year":"2011","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib35","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1128\/IAI.00424-15","article-title":"Toll-like receptor 9-mediated inflammation triggers alveolar bone loss in experimental murine periodontitis","volume":"83","author":"Kim","year":"2015","journal-title":"Infect. Immun."},{"key":"10.1016\/j.jbc.2022.101603_bib36","doi-asserted-by":"crossref","first-page":"14.12.1","DOI":"10.1002\/0471142735.im1412s109","article-title":"Toll-like receptors","volume":"109","author":"Takeda","year":"2015","journal-title":"Curr. Protoc. Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib37","first-page":"3651","article-title":"TLR8 deficiency leads to autoimmunity in mice","volume":"120","author":"Demaria","year":"2010","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.jbc.2022.101603_bib38","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.4049\/jimmunol.180.3.1382","article-title":"Stimulation by TLR5 modulates osteoclast differentiation through STAT1\/IFN-beta","volume":"180","author":"Ha","year":"2008","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib39","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.4049\/jimmunol.169.3.1516","article-title":"Stimulation by Toll-like receptors inhibits osteoclast differentiation","volume":"169","author":"Takami","year":"2002","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib40","doi-asserted-by":"crossref","first-page":"23103","DOI":"10.1038\/srep23103","article-title":"TLR3-\/4-priming differentially promotes Ca2+ signaling and cytokine expression and Ca2+-dependently augments cytokine release in hMSCs","volume":"6","author":"Park","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jbc.2022.101603_bib41","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S8756-3282(03)00086-3","article-title":"Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease","volume":"33","author":"Bendre","year":"2003","journal-title":"Bone"},{"key":"10.1016\/j.jbc.2022.101603_bib42","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cytogfr.2003.10.005","article-title":"IL-6, RANKL, TNF-alpha\/IL-1: Interrelations in bone resorption pathophysiology","volume":"15","author":"Steeve","year":"2004","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.jbc.2022.101603_bib43","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1177\/0022034515589289","article-title":"Necrosis-induced TLR3 activation promotes TLR2 expression in gingival cells","volume":"94","author":"Mori","year":"2015","journal-title":"J.\u00a0Dent. Res."},{"key":"10.1016\/j.jbc.2022.101603_bib44","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1084\/jem.191.2.275","article-title":"Tumor necrosis factor \u03b1 stimulates osteoclast differentiation by a mechanism independent of the Odf\/rankl\u2013rank interaction","volume":"191","author":"Kobayashi","year":"2000","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.jbc.2022.101603_bib45","doi-asserted-by":"crossref","first-page":"5522","DOI":"10.4049\/jimmunol.181.8.5522","article-title":"The clathrin-mediated endocytic pathway participates in dsRNA-induced IFN-\u03b2 production","volume":"181","author":"Itoh","year":"2008","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib46","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.immuni.2005.12.012","article-title":"Double-stranded RNA-mediated TLR3 activation is enhanced by CD14","volume":"24","author":"Lee","year":"2006","journal-title":"Immunity"},{"key":"10.1016\/j.jbc.2022.101603_bib47","doi-asserted-by":"crossref","first-page":"5653","DOI":"10.4049\/jimmunol.1102144","article-title":"Antimicrobial peptides inhibit polyinosinic-polycytidylic acid-induced immune responses","volume":"187","author":"Hasan","year":"2011","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2022.101603_bib48","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/jb\/mvz033","article-title":"Toll-like receptor 7 regulates osteoclastogenesis in rheumatoid arthritis","volume":"166","author":"Kim","year":"2019","journal-title":"J.\u00a0Biochem."},{"key":"10.1016\/j.jbc.2022.101603_bib49","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.3389\/fmicb.2018.03174","article-title":"TLR3 regulated poly I:C-induced neutrophil extracellular traps and acute lung injury partly through p38 MAP kinase","volume":"9","author":"Gan","year":"2018","journal-title":"Front Microbiol."},{"key":"10.1016\/j.jbc.2022.101603_bib50","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41467-019-13756-4","article-title":"Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis","volume":"11","author":"Herster","year":"2020","journal-title":"Nat. Commun."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925822000436?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925822000436?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:19:51Z","timestamp":1758241191000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925822000436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["S0021925822000436"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2022.101603","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Endosomal TLR3 signaling in stromal osteoblasts induces prostaglandin E2\u2013mediated inflammatory periodontal bone resorption","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2022.101603","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"101603"}}