Settem Rajendra P, Honma Kiyonobu, Chinthamani Sreedevi, Kawai Toshihisa, Sharma Ashu
Department of Oral Biology, University at Buffalo, Buffalo, NY, United States.
Department of Periodontology, College of Dental Medicine, Nova Southeastern University (NSU), Fort Lauderdale, FL, United States.
Front Physiol. 2021 Sep 14;12:722859. doi: 10.3389/fphys.2021.722859. eCollection 2021.
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) mice orally infected with the periodontal pathogen . The RANKL mice were obtained by crossing Cd19-Cre knock-in mice with mice homozygous for conditional RANKL-flox allele (RANKL). 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 . The data showed that the RANKL producing B cells increased significantly in the -infected wild-type mice compared to the sham-infected mice. Moreover, -infection induced higher alveolar bone loss in the wild-type and RANKL mice compared to infection either in the B cell deficient (Jh) or the B-cell specific RANKL deletion (RANKL) mice. These data established that the oral-pathogen activated B cells contribute significantly to alveolar bone resorption RANKL production.
牙周炎是一种由细菌引起的炎症性疾病，可导致牙齿脱落。它是由免疫反应失调（主要由中性粒细胞、巨噬细胞、T细胞和B细胞介导）对包括牙槽骨在内的牙齿支持组织产生的破坏作用所致。具体而言，在发炎的牙龈部位浸润的、具有分泌RANKL和炎性细胞因子能力的B细胞被认为在牙槽骨吸收中起作用。然而，B细胞在牙槽骨吸收中的直接作用尚未得到充分认识。在本研究中，我们试图通过使用病原体诱导的牙周炎小鼠模型（该模型使用了B细胞靶向RANKL缺失的条件性敲除小鼠）来确定表达RANKL的B细胞在牙周炎中的作用。简而言之，评估野生型、B细胞缺陷型（Jh）或B细胞-RANKL缺失型（RANKL）小鼠经口腔感染牙周病原体后的牙槽骨丢失情况。RANKL小鼠是通过将Cd19-Cre敲入小鼠与条件性RANKL-flox等位基因纯合的小鼠（RANKL）杂交获得的。通过形态计量分析和颌骨破骨细胞活性来确定牙槽骨吸收情况。此外，还评估了活化效应B细胞的骨吸收潜能。数据显示，与假感染小鼠相比，感染后的野生型小鼠中产生RANKL的B细胞显著增加。此外，与B细胞缺陷型（Jh）或B细胞特异性RANKL缺失型（RANKL）小鼠的感染相比，感染诱导野生型和RANKL小鼠出现更高的牙槽骨丢失。这些数据表明，口腔病原体激活的B细胞通过产生RANKL对牙槽骨吸收有显著贡献。
