Department of Periodontal Medicine, Graduate School of Biomedical & Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Division of Rheumatology, Kurume University Medical Center, 155-1 Kokubu-machi, Kurume, 839-0863, Japan.
Arthritis Res Ther. 2018 Nov 3;20(1):247. doi: 10.1186/s13075-018-1744-3.
Epidemiological evidence to suggest that periodontal disease (PD) is involved in the progression of rheumatoid arthritis (RA) is increasing. The complement system plays a critical role in immune responses. C5a has been implicated in chronic inflammatory diseases, including PD and RA. Porphyromonas gingivalis is the major causative bacteria of PD and can produce C5a. Therefore, it is hypothesized that P. gingivalis infection is involved in the progression of RA by elevating C5a levels. In the present study, P. gingivalis-infected RA model mice were established to investigate the involvement of C5a.
SKG mice orally infected with P. gingivalis were immunized with intraperitoneal injection of laminarin (LA) to induce arthritis. Arthritis development was assessed by arthritis score (AS), bone destruction on the talus, histology, and serum markers of RA. In order to investigate the effects of serum C5a on bone destruction, osteoclast differentiation of bone marrow mononuclear cells was examined by using serum samples from each group of mice. The relationship between C5a levels and antibody titers to periodontal pathogens in patients with RA was investigated by enzyme-linked immunosorbent assay.
P. gingivalis oral infection increased AS, infiltration of inflammatory cells, bone destruction on the talus, and serum markers of RA in mice immunized with LA. The addition of serum from LA-injected mice with the P. gingivalis oral infection promoted osteoclast differentiation, and the addition of a neutralization antibody against C5a suppressed osteoclast differentiation. C5a levels of serum in RA patients with positive P. gingivalis antibody were elevated compared with those in RA patients with negative P. gingivalis antibody.
These results suggest that P. gingivalis infection enhances the progression of RA via C5a.
越来越多的流行病学证据表明，牙周病（PD）与类风湿关节炎（RA）的进展有关。补体系统在免疫反应中起着关键作用。C5a 已被牵连到慢性炎症性疾病中，包括 PD 和 RA。牙龈卟啉单胞菌是 PD 的主要致病细菌，可产生 C5a。因此，有人假设 P. gingivalis 感染通过升高 C5a 水平而参与 RA 的进展。在本研究中，建立了 P. gingivalis 感染的 RA 模型小鼠来研究 C5a 的参与。
用牙龈卟啉单胞菌经口感染 SKG 小鼠，并用腹腔注射裂糊精（LA）诱导关节炎。通过关节炎评分（AS）、距骨骨破坏、组织学和 RA 的血清标志物评估关节炎的发展。为了研究血清 C5a 对骨破坏的影响，通过使用来自每组小鼠的血清样本检查了骨髓单核细胞的破骨细胞分化。通过酶联免疫吸附试验研究了 RA 患者中 C5a 水平与牙周病病原体抗体滴度之间的关系。
牙龈卟啉单胞菌经口感染增加了用 LA 免疫的小鼠的 AS、炎症细胞浸润、距骨骨破坏和 RA 的血清标志物。添加来自牙龈卟啉单胞菌经口感染的 LA 注射小鼠的血清促进了破骨细胞分化，而添加针对 C5a 的中和抗体抑制了破骨细胞分化。与具有阴性 P. gingivalis 抗体的 RA 患者相比，具有阳性 P. gingivalis 抗体的 RA 患者的血清 C5a 水平升高。
这些结果表明，P. gingivalis 感染通过 C5a 增强了 RA 的进展。
