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Objectives Neutrophil extracellular traps (NETs) play a role in the pathogenesis of periodontitis and rheumatoid arthritis (RA). However, it remains poorly understood whether NETs participate in the cross-talk between periodontitis and RA. Herein, we investigated the production of NETs in individuals with periodontitis and RA and its association with clinical parameters. The impact of periodontal therapy on RA and NET release was also assessed. Methods The concentration of NETs and cytokines was determined in the saliva and plasma of individuals with early RA (n = 24), established RA (n = 64), and individuals without RA (n = 76). The influence of periodontitis on the production of NETs and cytokines was also evaluated. Results Individuals with early RA had a higher concentration of NETs in saliva and plasma than individuals with established RA or without RA. Periodontitis resulted in an increase in the concentration of NETs of groups of individuals without RA and with early RA. The proportion of individuals with high concentrations of IL-6, IL-10 and GM-CSF was higher among individuals with periodontitis than among individuals without periodontitis. The concentrations of TNF-α, IL-6, IL-17/IL-25, and IL-28A were particularly high in individuals with early RA. Worse periodontal clinical parameters, RA onset and RA activity were significantly associated with circulating NETs. Periodontal therapy was associated with a reduction in the concentration of NETs and inflammatory cytokines and amelioration in periodontitis and RA. Conclusion This study reveals that NETs are a possible link between periodontitis and RA, with periodontal therapy resulting in a dramatic switch in circulating NET levels.

Studying effects of milk components on bone may have a clinical impact as milk is highly associated with bone maintenance, and clinical studies provided controversial associations with dairy consumption. We aimed to evaluate the impact of milk extracellular vesicles (mEVs) on the dynamics of bone loss in mice. MEVs are nanoparticles containing proteins, mRNA and microRNA, and were supplemented into the drinking water of mice, either receiving diet-induced obesity or ovariectomy (OVX). Mice receiving mEVs were protected from the bone loss caused by diet-induced obesity. In a more severe model of bone loss, OVX, higher osteoclast numbers in the femur were found, which were lowered by mEV treatment. Additionally, the osteoclastogenic potential of bone marrow-derived precursor cells was lowered in mEV-treated mice. The reduced stiffness in the femur of OVX mice was consequently reversed by mEV treatment, accompanied by improvement in the bone microarchitecture. In general, the RANKL/OPG ratio increased systemically and locally in both models and was rescued by mEV treatment. The number of osteocytes, as primary regulators of the RANKL/OPG system, raised in the femur of the OVX mEVs-treated group compared to OVX non-treated mice. Also, the osteocyte cell line treated with mEVs demonstrated a lowered RANKL/OPG ratio. Thus, mEVs showed systemic and local osteoprotective properties in two mouse models of bone loss reflected in reduced osteoclast presence. Data reveal mEV potential in bone modulation, acting via osteocyte enhancement and RANKL/OPG regulation. We suggest that mEVs could be a therapeutic candidate for the treatment of bone loss.

Aim This systematic review and meta‐analysis aimed to compare adipokines’ levels in gingival crevicular fluid (GCF) and saliva between individuals with obesity and individuals without obesity. Methods Computerized searches were conducted in four electronic databases (PubMed, Medline via Ovid, Web of Science, and Scopus). Manual searches and a Google Scholar search, limiting the search to the first 100 hits, were also conducted. Two calibrated authors performed the study selection, data extraction, and quality assessment of included articles. The quality of the included articles was evaluated using the University of Adelaide Tool. Results The electronic searches retrieved 929 titles/abstracts. Following the removal of duplicated references, 613 titles/abstracts were assessed. Thirty‐four articles were included. Meta‐analysis demonstrated that tumor necrosis factor‐α (TNF‐α) concentration in saliva was statistically increased in individuals with obesity compared with individuals without obesity (P < 0.05). By contrast, the meta‐analysis showed no difference in the concentrations of resistin, adiponectin, leptin, ghrelin, and interleukin 6 in saliva and of resistin, adiponectin, leptin, interleukin 6, interleukin 8, tumor necrosis factor α, and plasminogen activator inhibitor 1 in GCF between individuals with and without obesity (P > 0.05). Conclusions Individuals with obesity presented higher levels of TNF‐α in saliva than individuals without obesity. TNF‐α in saliva sampling may be a helpful marker for obesity. For the other adipokines, no difference was observed, but the limited availability and heterogeneity of data do not allow us to assertively state whether changes of adipokines in GCF and saliva are associated with obesity.