Departamento de Clínica, Patologia e Cirurgia Odontológicas, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
J Immunol. 2011 Oct 1;187(7):3821-30. doi: 10.4049/jimmunol.1101195. Epub 2011 Sep 2.
Rheumatoid arthritis (RA) and periodontal disease (PD) are prevalent chronic inflammatory disorders that affect bone structures. Individuals with RA are more likely to experience PD, but how disease in joints could induce PD remains unknown. This study aimed to experimentally mimic clinical parameters of RA-induced PD and to provide mechanistic findings to explain this association. Chronic Ag-induced arthritis (AIA) was triggered by injection of methylated BSA in the knee joint of immunized mice. Anti-TNF-α was used to assess the role of this cytokine. Intra-articular challenge induced infiltration of cells, synovial hyperplasia, bone resorption, proteoglycan loss, and increased expression of cytokines exclusively in challenged joints. Simultaneously, AIA resulted in severe alveolar bone loss, migration of osteoclasts, and release of proinflammatory cytokines in maxillae. Anti-TNF-α therapy prevented the development of both AIA and PD. AIA did not modify bacterial counts in the oral cavity. PD, but not AIA, induced by injection of Ag in immunized mice was decreased by local treatment with antiseptic, which decreased the oral microbiota. AIA was associated with an increase in serum C-reactive protein levels and the expression of the transcription factors RORγ and Foxp3 in cervical lymph nodes. There were higher titers of anti-collagen I IgG, and splenocytes were more responsive to collagen I in AIA mice. In conclusion, AIA-induced PD was dependent on TNF-α and the oral microbiota. Moreover, PD was associated with changes in expression of lymphocyte transcription factors, presence of anti-collagen Abs, and increased reactivity to autoantigens.
类风湿关节炎（RA）和牙周病（PD）是常见的慢性炎症性疾病，会影响骨骼结构。RA 患者更易患 PD，但关节疾病如何引发 PD 尚不清楚。本研究旨在通过实验模拟 RA 诱导 PD 的临床参数，并提供机制研究结果来解释这种关联。通过向免疫小鼠膝关节注射甲基化 BSA 来引发慢性 Ag 诱导性关节炎（AIA）。采用抗 TNF-α 来评估这种细胞因子的作用。关节内挑战会诱导细胞浸润、滑膜增生、骨质吸收、蛋白聚糖丢失以及细胞因子在受挑战关节中的表达增加。同时，AIA 导致上颌严重的牙槽骨丧失、破骨细胞迁移和促炎细胞因子的释放。抗 TNF-α 治疗可预防 AIA 和 PD 的发生。AIA 不会改变口腔中的细菌计数。在免疫小鼠中，通过注射 Ag 引发的 PD 而不是 AIA，局部使用防腐剂治疗可降低 PD 的发生率，从而减少口腔微生物群。AIA 与血清 C 反应蛋白水平升高以及颈淋巴结中转录因子 RORγ 和 Foxp3 的表达增加有关。AIA 小鼠的抗胶原 I IgG 滴度更高，且脾细胞对胶原 I 的反应性更强。总之，AIA 诱导的 PD 依赖于 TNF-α 和口腔微生物群。此外，PD 与淋巴细胞转录因子表达的变化、抗胶原 Abs 的存在以及对自身抗原的反应性增加有关。
