{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:59:21Z","timestamp":1783598361395,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"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":["JP20K09906"],"award-info":[{"award-number":["JP20K09906"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22KK0262"],"award-info":[{"award-number":["JP22KK0262"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K10096"],"award-info":[{"award-number":["JP20K10096"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019356","name":"SGH Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019356","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Cyst formation of the jaws is frequently accompanied by the proliferation of odontogenic epithelial cells located in the periodontal ligament (PDL), which consists of heterozygous cells and includes the most fibroblasts. The lining epithelium of radicular cyst, an odontogenic cyst of inflammatory origin, is derived from the proliferation of the remnants of the Hertwig epithelial root sheath (odontogenic epithelial cell rests of Malassez; ERMs) in the PDL. ERMs are maintained at a lower proliferative state under physiological conditions, but the regulatory mechanisms underlying the inflammation\u2010dependent enhanced\u2010proliferative capabilities of ERMs are not fully understood. The aim of this study was to evaluate the effects of cytokine pathway association between TGF\u2010\u03b2 signalling and IL\u20101\u03b2 signalling on the regulation of odontogenic epithelial cell proliferation using radicular cyst pathological specimens and odontogenic epithelial cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Immunofluorescence analyses were performed to clarify the expression levels of Smad2\/3 and Ki\u201067 in ERMs of 8\u2010week\u2010old mouse molar specimens. In radicular cyst (<jats:italic>n<\/jats:italic>\u2009=\u200952) and dentigerous cysts (<jats:italic>n<\/jats:italic>\u2009=\u20096) specimens from human patients, the expression of p65 (a main subunit of NF\u2010\u03baB), Smad2\/3 and Ki\u201067 were investigated using immunohistochemical analyses. Odontogenic epithelial cells and PDL fibroblastic cells were co\u2010cultured with or without an inhibitor or siRNAs. Odontogenic epithelial cells were cultured with or without TGF\u2010\u03b21 and IL\u20101\u03b2. The proliferative capabilities and Smad2 phosphorylation levels of odontogenic epithelial cells were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunohistochemically, Smad2\/3\u2010positivity was increased, and p65\u2010positivity and Ki\u201067\u2010positivity were decreased both in ERMs and in the epithelial cells in dentigerous cysts, a non\u2010inflammatory developmental cyst. In contrast, p65\u2010positive cells, along with the expression of Ki\u201067, were increased and Smad2\/3\u2010positive cells were decreased in the lining epithelia of radicular cysts. Co\u2010culture experiments with odontogenic epithelial cells and PDL fibroblastic cells revealed that PDL cells\u2010derived TGF\u2010\u03b21\/2 and their downstream signalling suppressed odontogenic epithelial cell proliferation. Moreover, TGF\u2010\u03b21 stimulation induced Smad2 phosphorylation and suppressed odontogenic epithelial cell proliferation, while IL\u20101\u03b2 stimulation reversed these phenotypes through p65 transactivation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that IL\u20101\u03b2\u2010p65 signalling promotes odontogenic epithelial cell proliferation through suppressing TGF\u2010\u03b2\u2010Smad2 signalling, which would be involved in the pathogenesis of radicular cysts.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.14016","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T06:43:40Z","timestamp":1704955420000},"page":"344-354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The <scp>IL<\/scp>\u20101\u03b2\u2010p65 axis stimulates quiescent odontogenic epithelial cell rests via <scp>TGF<\/scp>\u2010\u03b2 signalling to promote cell proliferation of the lining epithelia in radicular cysts: A laboratory investigation"],"prefix":"10.1111","volume":"57","author":[{"given":"Ryoko","family":"Nagano","sequence":"first","affiliation":[{"name":"Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science Kyushu University  Fukuoka Japan"},{"name":"Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Nakako","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science Kyushu University  Fukuoka Japan"},{"name":"Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8626-0193","authenticated-orcid":false,"given":"Shinsuke","family":"Fujii","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science Kyushu University  Fukuoka Japan"},{"name":"Dento\u2010Craniofacial Development and Regeneration Research Center, Faculty of Dental Science Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Kawano","sequence":"additional","affiliation":[{"name":"Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidefumi","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamotsu","family":"Kiyoshima","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science Kyushu University  Fukuoka 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