{"doi":"10.3389/fphys.2021.722859","title":"B-Cell RANKL Contributes to Pathogen-Induced Alveolar Bone Loss in an Experimental Periodontitis Mouse Model","abstract":"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 ΔB ) mice orally infected with the periodontal pathogen Tannerella forsythia . The RANKL ΔB mice were obtained by crossing Cd19-Cre knock-in mice with mice homozygous for conditional RANKL-flox allele (RANKL flox/flox ). 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 ex vivo . The data showed that the RANKL producing B cells increased significantly in the T. forsythia -infected wild-type mice compared to the sham-infected mice. Moreover, T. forsythia -infection induced higher alveolar bone loss in the wild-type and RANKL flox/flox mice compared to infection either in the B cell deficient (Jh) or the B-cell specific RANKL deletion (RANKL ΔB ) mice. These data established that the oral-pathogen activated B cells contribute significantly to alveolar bone resorption via RANKL production.","journal":"Frontiers in Physiology","year":2021,"id":167506,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":694999,"name":"Kiyonobu Honma","orcid":"0000-0003-1342-4745","position":1,"is_corresponding":false},{"id":695836,"name":"Sreedevi Chinthamani","orcid":null,"position":2,"is_corresponding":false},{"id":303716,"name":"Toshihisa Kawai","orcid":"0000-0003-3310-3818","position":3,"is_corresponding":false},{"id":695000,"name":"Ashu Sharma","orcid":"0000-0001-9252-0668","position":4,"is_corresponding":false},{"id":694998,"name":"Rajendra P. Settem","orcid":"0000-0002-3577-7675","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-18T23:45:58.359801Z","pmid":"34594237","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}