Neutrophil extracellular traps mediate bone erosion in rheumatoid arthritis by enhancing RANKL-induced osteoclastogenesis.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause bone erosion due to increased osteoclastogenesis. Neutrophils involvement in osteoclastogenesis remains uncertain. Given that neutrophil extracellular traps (NETs) can act as inflammatory mediators in rheumatoid arthritis, we investigated the role of NETs in stimulating bone loss by potentiating osteoclastogenesis during arthritis. EXPERIMENTAL APPROACH: The level of NETs in synovial fluid from arthritis patients was assessed. Bone loss was evaluated by histology and micro-CT in antigen-induced arthritis (AIA)-induced WT mice treated with DNase or in Padi4-deficient mice (Padi4flox/flox LysMCRE ). The size and function of osteoclasts and the levels of RANKL and osteoprotegerin (OPG) released by osteoblasts that were incubated with NETs were measured. The expression of osteoclastogenic marker genes and protein levels were evaluated by qPCR and western blotting. To assess the participation of TLR4 and TLR9 in osteoclastogenesis, cells from Tlr4-/- and Tlr9-/- mice were cultured with NETs. KEY RESULTS: Rheumatoid arthritis patients had higher levels of NETs in synovial fluid than osteoarthritis patients, which correlated with increased levels of RANKL/OPG. Moreover, patients with bone erosion had higher levels of NETs. Inhibiting NETs with DNase or Padi4 deletion alleviated bone loss in arthritic mice. Consistently, NETs enhanced RANKL-induced osteoclastogenesis that was dependent on TLR4 and TLR9 and increased osteoclast resorptive functions in vitro. In addition, NETs stimulated the release of RANKL and inhibited osteoprotegerin in osteoblasts, favouring osteoclastogenesis. CONCLUSIONS AND IMPLICATIONS: Inhibiting NETs could be an alternative strategy to reduce bone erosion in arthritis patients.

Tumor Necrosis Factor-alpha in Gingival Crevicular Fluid as a Diagnostic Marker for Periodontal Diseases: A Systematic Review.

OBJECTIVES: The aim of this systematic review was to evaluate human gingival crevicular fluid (GCF) tumor necrosis factor-alpha (TNF-α) as a potential biomarker for diagnosis of periodontal disease (International prospective register of systematic reviews [PROSPERO] number: CRD42015020199). METHODS: An electronic search for TNF-α in human GCF was conducted until May 17, 2018. Data from systemically healthy patients with healthy periodontium or periodontal disease were incorporated. Risk bias was assessed by Newcastle-Ottawa Scale for case-control studies and Jadad scale for clinical trials. RESULTS: Twenty-six studies were included (12 case-control studies, 7 clinical trials, and 7 randomized controlled trials). Most case-control studies showed increased TNF-α concentration in GCF of patients with periodontal disease. The clinical trials and randomized controlled trials demonstrated no consistent modification of TNF-α level after periodontal intervention. CONCLUSION: The present data support the use of TNF-α in GCF as a potential biomarker for diagnosis of periodontal disease but not to monitor the healing after therapy.

Nickel-free vs conventional braces for patients allergic to nickel: Gingival and blood parameters during and after treatment.

INTRODUCTION: Allergic and inflammatory reactions have commonly been associated with the release of metal ions during orthodontic treatment. Our objective was to evaluate prospectively gingival and blood status in patients allergic to nickel. METHODS: Allergy to nickel was diagnosed using a patch test. Two groups were established: conventional braces (n = 21) and nickel-free braces (n = 21). The gingival index was used to determine gingival status before treatment, periodically for 12 months (evaluations every 3 months), and 1 month after the removal of the braces. Blood status was evaluated with a complete blood count, including the quantification of nickel and immunoglobin E before treatment, during treatment, and 1 month after removal of the braces. The data were analyzed using Mann-Whitney, Student t, Wilcoxon, repeated measures analysis of variance, Friedman, and chi-square tests. Either the Pearson or the Spearman correlation coefficients were calculated, when appropriate. RESULTS: The number of basophils increased significantly among the evaluations in both groups (conventional, P = 0.002; nickel-free, P = 0.001), whereas the number of eosinophils and the immunoglobin E levels decreased significantly in the conventional group (P = 0.004). Plasma nickel levels were increased before and during treatment, and decreased 1 month after removing the braces in both groups, but the differences were significant only in the nickel-free group (P = 0.002). No correlations were found between the concentrations of nickel and immunoglobin E, basophils, or eosinophils, or between the gingival index and either bands or segmented neutrophils (P ≥ 0.05). CONCLUSIONS: Patients treated with nickel-free braces had better gingival health and smaller blood changes than did those treated with conventional braces. All abnormalities tended to be eliminated after the removal of the braces.