Background: The objective of this systematic review and meta-analysis was to evaluate the effects of non-surgical periodontal therapy (NSPT) on inflammatory-related cytokines/adipocytokines in periodontitis patients with or without obesity. Methods: We followed the preferred reporting items for systematic reviews and meta-analyses statement and registered the study (CRD42022375331) in the Prospective International Register of Systematic Reviews. We screened randomized-controlled trials and controlled clinical trials from six databases up to December 2022. Quality assessment was performed with RoB-2 and ROBINS-I tools for randomized trials and non-randomized trials, respectively. Meta-analysis was carried out using a random-effect model. Results: We included seventeen references in the systematic analysis, and sixteen in the meta-analysis. Baseline results of pro-inflammatory biomarkers, including serum interleukin (IL)-6, serum and gingival crevicular fluid (GCF), tumor necrosis factor (TNF)-a, serum C-reactive protein (CRP)/hs-CRP, and serum and GCF resistin, were higher in obesity subjects than in normal weight subjects. The effect of NSPT with respect to levels of cytokines/adipocytokines, including IL-6, TNF-a, CRP/hs-CRP, resistin, adiponectin, leptin and retinol binding protein 4 (RBP4), were then analyzed in the systematic and meta-analysis. After three months of NSPT, serum (MD = -0.54, CI = -0.62 – -0.46), and GCF (MD = -2.70, CI = -4.77 – -0.63) levels of IL-6, along with the serum RBP4 (MD = -0.39, CI = -0.68–0.10) decreased in periodontitis individuals with obesity. NSPT also improved GCF adiponectin levels after three months (MD = 2.37, CI = 0.29 – 4.45) in periodontitis individuals without obesity. Conclusions: Obese status altered the baseline levels of cytokines/adipocytokines (serum IL-6, serum and GCF TNF-a, serum CRP/hs-CRP, and serum and GCF resistin). Then NSPT can shift the levels of specific pro-inflammatory mediators and anti-inflammatory mediators in biological fluids, both in obesity and non-obesity individuals. NSPT can reduce serum and GCF IL-6 levels together with serum RBP4 level in individuals with obesity after 3 months, besides, there is no sufficient evidence to prove that obese patients have a statistically significant decrease in the levels of other cytokines compared to patients with normal weight. NSPT can also increase GCF adiponectin level in normal weight individuals after 3 months. Our findings imply the potential ideal follow-up intervals and sensitive biomarkers for clinical bioanalysis in personalized decision-making of effect of NSPT due to patients’ BMI value.

Background: Appropriate mechanical stimulation is essential for bone homeostasis in healthy periodontal tissues. While the osteogenesis and osteoclast differentiation of inflammatory periodontal ligament cells under different dynamic loading has not been yet clear. The aim of this study is to clarify the inflammatory, osteogenic and pro-osteoclastic effects of different cyclic stress loading on the inflammatory human periodontal ligament cells (hPDLCs).Methods: hPDLCs were isolated from healthy premolars and cultured in alpha minimum Eagle’s medium (α-MEM). Lipopolysaccharides (LPS) were used to induce the inflammation state of hPDLCs in vitro. Determination of LPS concentration for the model of inflammatory periodontium was based on MTT and genes expression analysis. Then the cyclic stress of 0, 0–50, 0–90 and 0–150 kPa was applied to the inflammatory hPDLCs for 5 days respectively. mRNA and protein levels of osteogenic, osteoclastic and inflammation-related markers were examined after the treatment.Results: MTT and RT-PCR results showed that 10 μg/ml LPS up-regulatedTNF-α, IL-1β, IL-6, IL-8andMCP-1mRNA levels (P < 0.05) and did not affect the cell viability (P > 0.05). The excessive loading of stress (150 kPa) with or without LPS strongly increased the expression of inflammatory-related markersTNF-α,IL-1β,IL-6,IL-8,MCP-1(P < 0.05) and osteoclastic markersRANKL,M-CSF,PTHLHandCTSKcompared with other groups (P < 0.05), but had no significant effect on osteogenic genes. While 0–90 kPa cyclic pressure could up-regulate the expression of osteogenic genesALP, COL-1,RUNX2, OCN, OPNandOSXin the healthy hPDLSCs.Conclusions: Collectively, it could be concluded that 0–150 kPa was an excessive stress loading which accelerated both inflammatory and osteoclastic effects, while 0–90 kPa may be a positive factor for the osteogenic differentiation of hPDLCs in vitro.

Background: To investigate the association between clinical periodontal parameters of periodontitis, serum lipid metabolism markers and adipokines’ levels in patients with obesity and periodontitis. Methods: A total of 112 patients admitted to Hospital of Xi’an Jiaotong University were included in this study. They were divided into normal body weight group (18.5 < body mass index, BMI < 25, n = 36), overweight group (25 ≤ BMI < 30, n = 38), and obesity group (BMI ≥ 30, n = 38) accordingly. The diagnosis of periodontitis was based on the newest international classification of periodontitis. Full-mouth clinical periodontal measurements included: plaque index, periodontal pocket depth, clinical attachment level, and bleeding on probing. Gingival crevicular fluid samples were analyzed for: Interleukin-1β, tumor necrosis factor-α, Interleukin-6 and C-reactive protein. Serum triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and glycosylated hemoglobin levels were measured. Visfatin, leptin, resistin, and adiponectin levels in serum were also measured. Results: The ratio of participants without periodontitis was significantly highest in normal weight group, and the proportion of severe periodontitis (stage III and IV) was highest in obesity group. The periodontal pocket depth, clinical attachment level, and the inflammatory cytokines in gingival crevicular fluid in obesity group and overweight group were higher than those in normal body weight group. The BMI and waist-to-hip ratio (WHR) were significantly positive correlated with periodontal pocket depth and clinical attachment level. Using a Multivariate logistic regression model, periodontitis correlates to BMI, WHR, serum levels of triglyceride, total cholesterol, low density lipoprotein, and adipokines such as visfatin, leptin, and resistin. Conclusions: Obesity is positively correlated with the aggravation of periodontitis. Obesity may aggravate the damage to periodontal tissue by regulating the secretion level of adipokines.

There is a significant comorbidity between obesity and periodontitis, while adipokines are pivotal in the immunoinflammatory process, which may play a role in this special relationship. We aimed to assess the effect of adipokines as mediators in the progression of periodontitis in obese Sprague Dawley rats. Rats were divided into four groups: normal body weight with and without periodontitis and obesity with and without periodontitis. Experimental obesity and periodontitis were induced by a high-fat diet or ligaturing, and the effect was measured using metabolic and micro-computed tomography analysis and histological staining. Compared with the other three groups, the group of periodontitis with obesity (OP) had the heaviest alveolar bone absorption, the largest increase in osteoclasts, the utmost inflammatory cell infiltration and the highest expressions of pro-inflammatory cytokines and nuclear factor-kappa B ligand (RANKL); meanwhile, its expression of the osteogenesis-related gene was the lowest among the four groups. The expressions of leptin, visfatin, resistin, retinol-binding protein 4 (RBP4) and asprosin were upregulated, while adiponectin was decreased significantly in OP. The strong positive associations between the periodontal or circulating levels of RBP4 (or asprosin) and the degree of alveolar resorption in experimental periodontitis and obese rats were revealed. The upregulated expression of inflammation biomarkers, the corresponding degradation in connective tissue and the generation of osteoclasts in periodontitis were activated and exacerbated in obesity. The elevated level of RBP4/asprosin may contribute to a more severe periodontal inflammatory state in obese rats.

Introduction: Orthodontic pain is the most common adverse side effect reported in the context of tooth movement. Given its central role in processing pain and negative emotion, the central nucleus of the amygdala (CeA) is thought to be a key site involved in orthodontic pain sensation.Methods: In the present study, we therefore explored whether the CeA is involved in contributing to orthodontic pain in a rat model of tooth movement. For this study, we utilized adult male rats with bilateral sham or electrolytic CeA lesions (400 μA; 25 s), and then we analyzed face grooming behavior as a measure of pain sensation.Results: Through this approach, we found that there were time‐ and force‐dependent factors influencing pain levels in these rats. We further found that bilateral CeA lesions markedly reduced tooth movement‐induced orofacial pain and that unilateral CeA lesions did so to a lesser extent.Conclusions: As such, these results suggest the CeA is a key area of orthodontic pain, with the results of this study highlighting potential avenues for achieving pain relief in those suffering from orthodontic pain.