Porphyromonas gingivalis Infection-Associated Periodontal Bone Resorption Is Dependent on Receptor Activator of NF-κB Ligand

Han, Xiaozhe; Lin, Xiaoping; Yu, Xiaoqian; Lin, Jiang; Kawai, Toshihisa; LaRosa, Karen B.; Taubman, Martin A.

doi:10.1128/iai.00043-13

Cited by 60 publications

(60 citation statements)

References 35 publications

(52 reference statements)

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“…In the current study, in line with previously reported data [68] P. gingivalis DNA was detected in the oral cavity of the periodontitis-affected animals, although the presence of P. gingivalis in metacarpophalangeal joint tissue of periodontitis-affected animals could not be detected. To our knowledge, P. gingivali s DNA in synovial tissue in experimental animal models has not yet been reported.…”

Section: Discussionsupporting

confidence: 92%

Effects by periodontitis on pristane-induced arthritis in rats

Eriksson¹,

Lönnblom²,

Tour³

et al. 2016

J Transl Med

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BackgroundAn infection-immune association of periodontal disease with rheumatoid arthritis has been suggested. This study aimed to investigate the effect of pre-existing periodontitis on the development and the immune/inflammatory response of pristane-induced arthritis.MethodsWe investigated the effect of periodontitis induced by ligature placement and Porphyromonas gingivalis (P. gingivalis) infection, in combination with Fusobacterium nucleatum to promote its colonization, on the development of pristane-induced arthritis (PIA) in rats (Dark Agouti). Disease progression and severity of periodontitis and arthritis was monitored using clinical assessment, micro-computed tomography (micro-CT)/intraoral radiographs, antibody response, the inflammatory markers such as α-1-acid glycoprotein (α-1-AGP) and c-reactive protein (CRP) as well as cytokine multiplex profiling at different time intervals after induction.ResultsExperimentally induced periodontitis manifested clinically (P < 0.05) prior to pristane injection and progressed steadily until the end of experiments (15 weeks), as compared to the non-ligated arthritis group. Injection of pristane 8 weeks after periodontitis-induction led to severe arthritis in all rats demonstrating that the severity of arthritis was not affected by the pre-existence of periodontitis. Endpoint analysis showed that 89% of the periodontitis-affected animals were positive for antibodies against arginine gingipain B and furthermore, the plasma antibody levels to a citrullinated P. gingivalis peptidylarginine deiminase (PPAD) peptide (denoted CPP3) were significantly (P < 0.05) higher in periodontitis rats with PIA. Additionally, there was a trend towards increased pro-inflammatory and anti-inflammatory cytokine levels, and increased α-1-AGP levels in plasma from periodontitis-challenged PIA rats.ConclusionsPre-existence of periodontitis induced antibodies against citrullinated peptide derived from PPAD in rats with PIA. However, there were no differences in the development or severity of PIA between periodontitis challenged and periodontitis free rats.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1067-6) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Effects by periodontitis on pristane-induced arthritis in rats

Eriksson¹,

Lönnblom²,

Tour³

et al. 2016

J Transl Med

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“…Our previous rat models of periodontal disease showed similar results, i.e., the levels of RANKL mRNA and protein expression positively correlated with the level of bone resorption, and RANKL blockage by anti-RANKL antibody led to significantly decreased bone loss (40,41). In this study, the decreased RANKL/ OPG ratio in mouse gingival tissue injected with anti-RANKL antibody further substantiated the effect of RANKL blockage in the bone resorption process (Fig.…”

Section: Discussionsupporting

confidence: 65%

Porphyromonas gingivalis Exacerbates Ligature-Induced, RANKL-Dependent Alveolar Bone Resorption via Differential Regulation of Toll-Like Receptor 2 (TLR2) and TLR4

Lin

et al. 2014

Infect Immun

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dToll-like receptors (TLRs) play a key role in the innate immune responses to periodontal pathogens in periodontal disease. The present study was performed to determine the roles of TLR2 and TLR4 signaling in alveolar bone resorption, using a Porphyromonas gingivalis-associated ligature-induced periodontitis model in mice. Wild-type (WT), Tlr2 ؊/؊ , and Tlr4 ؊/؊ mice (8 to 10 weeks old) in the C57/BL6 background were used. Silk ligatures were applied to the maxillary second molars in the presence or absence of live P. gingivalis infection. Ligatures were removed from the second molars on day 14, and mice were kept for another 2 weeks before sacrifice for final analysis (day 28). On day 14, there were no differences in alveolar bone resorption and gingival RANKL expression between mice treated with ligation plus P. gingivalis infection and mice treated with ligation alone. Gingival interleukin-1␤ (IL-1␤) and tumor necrosis factor alpha (TNF-␣) expression was increased, whereas IL-10 expression was decreased in WT and Tlr2 ؊/؊ mice but not in Tlr4 ؊/؊ mice. On day 28, WT and Tlr4 ؊/؊ mice treated with ligation plus P. gingivalis infection showed significantly increased bone loss and gingival RANKL expression compared to those treated with ligation alone, whereas such an increase was diminished in Tlr2 ؊/؊ mice. Gingival TNF-␣ upregulation and IL-10 downregulation were observed only in WT and Tlr4 ؊/؊ mice, not in Tlr2 ؊/؊ mice. In all mice, bone resorption induced by ligation plus P. gingivalis infection was antagonized by local anti-RANKL antibody administration. This study suggests that P. gingivalis exacerbates ligature-induced, RANKL-dependent periodontal bone resorption via differential regulation of TLR2 and TLR4 signaling.

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“…RANKL blockade has been successful in animal models of periodontitis (180)(181)(182). Patients treated with anti-TNF-α therapy for other disorders have also shown some improvement in alveolar bone loss (183).…”

Section: Therapeutic Perspectivementioning

confidence: 99%