{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T02:19:49Z","timestamp":1782872389568,"version":"3.54.5"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>This is the first study to our knowledge to report a novel mutation in the interferon regulatory factor 8 gene (IRF8G388S) associated with multiple idiopathic tooth root resorption, a form of periodontal disease. The IRF8G388S variant in the highly conserved C-terminal motif is predicted to alter the protein structure, likely impairing IRF8 function. Functional assays demonstrated that the IRF8G388S mutant promoted osteoclastogenesis and failed to inhibit NFATc1-dependent transcriptional activation when compared with IRF8WT control. Further, similar to subjects with heterozygous IRF8G388S mutation, Irf8+\/\u2013 mice exhibited increased osteoclast activity in the mandibular alveolar bone surrounding molar teeth. Immunohistochemistry illustrated increased NFATc1 expression in the dentoalveolar region of Irf8\u2013\/\u2013 and Irf8+\/\u2013 mice when compared with Irf8+\/+ controls. Genomewide analyses revealed that IRF8 constitutively bound to regulatory regions of several thousand genes in osteoclast precursors, and genetic aberration of IRF8 significantly enhanced many osteoclast-specific transcripts. Collectively, this study delineates the critical role of IRF8 in defining osteoclast lineage and osteoclast transcriptional program, which may help in better understanding of various osteoclast-mediated disorders, including periodontal disease. \u00a9 2019 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3690","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T20:41:15Z","timestamp":1551904875000},"page":"1155-1168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Inactivating Mutation in <i>IRF8<\/i> Promotes Osteoclast Transcriptional Programs and Increases Susceptibility to Tooth Root Resorption"],"prefix":"10.1093","volume":"34","author":[{"given":"Vivek","family":"Thumbigere-Math","sequence":"first","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) National Institutes of Health (NIH) BethesdaMD USA"},{"name":"Division of Periodontology University of Maryland School of Dentistry BaltimoreMD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L","family":"Foster","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry The Ohio State University ColumbusOH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Bachu","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH BethesdaMD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Yoshii","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH BethesdaMD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Brooks","sequence":"additional","affiliation":[{"name":"National 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