osteoprotegerin and Aggressive-Periodontitis

Although dental implants and bone regenerative procedures are important approaches for the reestablishment of esthetics and function in young patients with a history of generalized aggressive periodontitis (GAP), no predictable outcomes have been reported, and the host osteo-immunoinflammatory response may play a relevant role in this context. In view of the lack of molecular investigations into the bone tissue condition of young patients with periodontitis, the aim of this study was to evaluate the gene expression of bone-related factors in this population. Bone biopsies were obtained from the posterior mandible in 16 individuals previously diagnosed with GAP and on periodontal support therapy and from 17 periodontally healthy (PH) patients. The gene expression of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, receptor activator of the NF-κB ligand (RANKL), osteoprotegerin (OPG), osteocalcin (OC), bone sialoprotein (BSP), and type I collagen (COL-I), important biomarkers of bone turnover, was evaluated by qRT-PCR. Lower TGF-β and OPG mRNA levels were observed in GAP patients compared to PH individuals (p ≤ 0.05). There were no between-group differences in levels of TNF-α, BSP, RANKL, OC, or COL-I mRNA (p>0.05). In young adults, a history of periodontal disease can negatively modulate the gene expression of important bone-related factors in alveolar bone tissue. These molecular outcomes may contribute to the future development of therapeutic approaches to benefit bone healing in young patients with history of periodontitis via modulation of osteo-immuno-inflammatory biomarkers.

Topics: Adult; Aggressive Periodontitis; Alveolar Process; Biomarkers; Collagen Type I; Cross-Sectional Studies; Female; Gene Expression; Humans; Integrin-Binding Sialoprotein; Male; Osteocalcin; Osteoprotegerin; RANK Ligand; Real-Time Polymerase Chain Reaction; Reference Values; Single-Blind Method; Statistics, Nonparametric; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Young Adult

In this study, the relationships between total oxidant status (TOS) and receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) levels and RANKL/OPG ratios in serum and gingival crevicular fluid (GCF) are investigated in patients with chronic (CP) and generalized aggressive (GAgP) periodontitis.. Thirty patients with CP, 30 patients with GAgP, and 28 periodontally healthy controls were included in the study. After clinical measurements and samplings, serum and GCF TOS, RANKL, and OPG levels were determined by a novel automatic colorimetric method and enzyme-linked immunosorbent assays.. Serum and GCF TOS, RANKL, and RANKL/OPG values were higher in the periodontitis groups compared with controls, and they were also higher in the GAgP group than the CP group (except serum and GCF RANKL). Furthermore, serum and GCF OPG concentrations were lower in the periodontitis groups than in controls. Strong positive and negative correlations were observed between the periodontal parameters TOS and bone resorption biomarkers.. The present results reveal that TOS, RANKL, and RANKL/OPG values are systemically and locally increased in periodontitis and that this increase is more evident in AgP than CP. These findings further suggest that oxidative stress is closely associated with the severity of periodontitis and bone resorption biomarkers.

Topics: Adult; Aggressive Periodontitis; Alveolar Bone Loss; Biomarkers; Chronic Periodontitis; Dental Plaque Index; Female; Gingival Crevicular Fluid; Humans; Male; Osteoprotegerin; Oxidants; Oxidative Stress; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; RANK Ligand; Reactive Oxygen Species; Young Adult

Among the innate defense mechanisms in the oral cavity, lactoferrin (LF) is a vital antimicrobial that can modify the host response against periodontopathogens. Aggregatibacter actinomycetemcomitans is the main periodontopathogen of localized aggressive periodontitis. The aim of this study is to evaluate the role of LF during A. actinomycetemcomitans-induced periodontitis.. Differences in the expression levels of cytokines, chemokines, chemokine receptors, and bone loss markers between wild-type (WT) and LF knockout mice (LFKO(-/-)) were evaluated by real time-PCR. Serum IgG and LF levels were quantified by ELISA. Alveolar bone loss among the groups was estimated by measuring the distance from cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) at 20 molar sites.. Oral infection with A. actinomycetemcomitans increased LF levels in periodontal tissue (P = 0.01) and saliva (P = 0.0004) of wild-type infected (WTI) mice compared to wild-type control mice. Pro-inflammatory cytokines such as interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-12 were increased in the infected LF knockout (LFKO(-/-)I) mice compared to the WTI mice, whereas the anti-inflammatory cytokines IL-4 and IL-10 were decreased. Chemokines and chemokine receptors showed different expression patterns between WTI and LFKO(-/-)I mice. The LFKO(-/-)I mice developed increased bone loss (P = 0.002), in conjunction with increased expression of receptor activator of nuclear factor-κB ligand and decrease in osteoprotegerin, compared to WTI mice.. These results demonstrate that the infected LFKO(-/-) mice were more susceptible to A. actinomycetemcomitans-induced alveolar bone loss, with different patterns of immune responses compared to those of WTI mice.

Topics: Aggregatibacter actinomycetemcomitans; Aggressive Periodontitis; Alveolar Bone Loss; Animals; Chemokines; Cytokines; Disease Susceptibility; Immunoglobulin G; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukins; Lactoferrin; Mice; Mice, Knockout; Osteoprotegerin; Pasteurellaceae Infections; Periodontium; RANK Ligand; Receptors, Chemokine; Saliva; Tooth Cervix; Tumor Necrosis Factor-alpha; Vesicular Transport Proteins

Receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) have an established role in the pathogenesis of periodontitis, which is characterized by an increased RANKL/OPG ratio. The present study aims to investigate changes of RANKL, OPG and their relative ratio in gingival crevicular fluid (GCF) of periodontitis patients after non-surgical periodontal treatment.. GCF was obtained from chronic periodontitis (n=14), generalized aggressive periodontitis (G-AgP; n=13) patients at baseline. The patients received scaling and root planing and were recalled after 2, 3 and 4 months for follow-up clinical examination and sampling. The total amounts and concentrations of RANKL and OPG in GCF were measured by enzyme-linked immunosorbent assay, and their relative ratio was calculated.. The RANKL/OPG ratio remained unchanged and did not correlate with clinical parameters throughout the monitoring period, despite the improved clinical outcome. This trend was similar in both chronic and G-AgP.. Although the RANKL/OPG ratio has a potential diagnostic value for untreated periodontitis, it may not be a suitable predictor of clinically successful treatment outcome. As conventional therapy does not negatively modulate this ratio, the host could still be susceptible to further periodontal tissue destruction, warranting the consideration of adjunctive treatments.

Topics: Adolescent; Adult; Aggressive Periodontitis; Biomarkers; Chronic Periodontitis; Dental Prophylaxis; Female; Gingival Crevicular Fluid; Humans; Longitudinal Studies; Male; Middle Aged; Osteoprotegerin; RANK Ligand; Treatment Outcome; Young Adult