{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:08:34Z","timestamp":1791590914305,"version":"4.3.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Periodontitis is a bacterially-induced inflammatory disease that leads to tooth loss. It results from the damaging effects of a dysregulated immune response, mediated largely by neutrophils, macrophages, T cells and B cells, on the tooth-supporting tissues including the alveolar bone. Specifically, infiltrating B cells at inflamed gingival sites with an ability to secrete RANKL and inflammatory cytokines are thought to play roles in alveolar bone resorption. However, the direct contribution of B cells in alveolar bone resorption has not been fully appreciated. In this study we sought to define the contribution of RANKL expressing B cells in periodontitis by employing a mouse model of pathogen-induced periodontitis that used conditional knockout mice with B cell-targeted RANKL deletion. Briefly, alveolar bone loss was assessed in the wild-type, B-cell deficient (Jh), or B-cell-RANKL deleted (RANKL<jats:sup>\u0394B<\/jats:sup>) mice orally infected with the periodontal pathogen <jats:italic>Tannerella forsythia<\/jats:italic>. The RANKL<jats:sup>\u0394B<\/jats:sup> mice were obtained by crossing Cd19-Cre knock-in mice with mice homozygous for conditional RANKL-flox allele (RANKL<jats:sup>flox\/flox<\/jats:sup>). The alveolar bone resorption was determined by morphometric analysis and osteoclastic activity of the jaw bone. In addition, the bone resorptive potential of the activated effector B cells was assessed <jats:italic>ex vivo<\/jats:italic>. The data showed that the RANKL producing B cells increased significantly in the <jats:italic>T. forsythia<\/jats:italic>-infected wild-type mice compared to the sham-infected mice. Moreover, <jats:italic>T. forsythia<\/jats:italic>-infection induced higher alveolar bone loss in the wild-type and RANKL<jats:sup>flox\/flox<\/jats:sup> mice compared to infection either in the B cell deficient (Jh) or the B-cell specific RANKL deletion (RANKL<jats:sup>\u0394B<\/jats:sup>) mice. These data established that the oral-pathogen activated B cells contribute significantly to alveolar bone resorption <jats:italic>via<\/jats:italic> RANKL production.<\/jats:p>","DOI":"10.3389\/fphys.2021.722859","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T05:08:55Z","timestamp":1631596135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":36,"title":["B-Cell RANKL Contributes to Pathogen-Induced Alveolar Bone Loss in an Experimental Periodontitis Mouse Model"],"prefix":"10.3389","volume":"12","author":[{"given":"Rajendra P.","family":"Settem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyonobu","family":"Honma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreedevi","family":"Chinthamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashu","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.4049\/jimmunol.1500496","article-title":"The B Cell-Stimulatory Cytokines BLyS and APRIL Are Elevated in Human Periodontitis and Are Required for B Cell-Dependent Bone Loss in Experimental Murine Periodontitis.","volume":"195","author":"Abe","year":"2015","journal-title":"J. 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