Total Oxidant Status and Bone Resorption Biomarkers in Serum and Gingival Crevicular Fluid of Patients With Periodontitis

• Autores: Esra Baltacioglu
• Localización: Journal of periodontology, ISSN 0022-3492, Nº. 2, 2014, págs. 317-326
• Idioma: inglés
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• Resumen

  • Background: In this study, the relationships between total oxidant status (TOS) and receptor activator of nuclear factor-?B 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.

    Methods: 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.

    Results: 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.

    Conclusions: 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.

    In association with chronic inflammation, chronic (CP) and aggressive (AgP) periodontitis destroy periodontal connective tissue and bone, threatening not only dentition but also general health.1 Pathogenic bacteria are the major causative factors in the initiation and progression of periodontitis. However, pathogens do not directly cause breakdown; instead, the damage occurs as a result of the complex interaction between the microbial challenge and host immunoinflammatory responses.2 In addition, activation of the immune system and production of reactive oxygen species (ROS) are known to be involved in the pathophysiologic progression of periodontal diseases.2,3 ROS are highly reactive derivatives of oxygen metabolism that have emerged as important signaling molecules in various cellular processes.3,4 As a host defense mechanism against bacterial pathogens, the production of ROS is essential in diseases associated with phagocytic infiltration.5-7 However, if not neutralized by antioxidant systems, ROS have the potential to cause significant damage and impair a wide variety of biologic molecules, including lipids, proteins, and DNA.4-6 Increased production of ROS may contribute to oxidative stress, which is an important physiologic modifier of immune and inflammatory mechanisms.8 A large body of evidence supports the role of oxidative stress in the pathogenesis of many human diseases and metabolic bone diseases, such as osteoporosis and, more recently, periodontitis.9-13 Immunoinflammatory responses play an important role in periodontal bone breakdown in hosts susceptible to periodontal disease.14-16 The relationship between the immune system and bone metabolism, termed �osteoimmunology,� is a rapidly evolving field of investigation.15 Understanding osteoimmunology will provide new insights into the pathogenic mechanisms of bone resorption and facilitate elucidation of the etiology of periodontitis and other inflammatory bone diseases.14,15 The role of the host response in periodontal bone loss is complex.15,16 Briefly, a fundamental characteristic of inflammatory bone breakdown in periodontitis is enhanced osteoclast activity without a corresponding increase in bone formation.1,14,17 Receptor activator of nuclear factor-?B ligand (RANKL) is a key mediator involved in physiologic osteoclastogenesis and pathologic bone loss.14,17 Osteoprotegerin (OPG), a natural inhibitor of RANKL, acts as a decoy and blocks the binding of RANKL to receptor activator of nuclear factor-?B (RANK), thus preventing osteoclastogenesis.1 Therefore, inflammatory bone breakdown is regulated by the molecular interplay between RANKL, RANK, and OPG; these principal molecules are related to the tumor necrosis factor ligand and receptor families.1,14 The RANKL�RANK�OPG axis and its regulation are of critical importance in certain inflammatory bone conditions.15 A relative decrease in OPG concentrations or an increase in RANKL expression may result in a net increase in RANKL and pathologic bone resorption, also known as an increase in the RANKL/OPG ratio.15,17 Current research indicates that RANKL concentrations increase, OPG levels remain unchanged or decrease, and the RANKL/OPG ratio is increased in gingival tissues and gingival crevicular fluid (GCF) in individuals with periodontitis compared with healthy controls.18-23 The significant increase in the RANKL/OPG ratio in gingivitis and GCF in periodontitis may be associated with increased bone loss and disease severity.15,17 ROS play an important role in the mechanism of bone resorption.24,25 An increase in ROS and a decrease in the antioxidation system can contribute to bone resorption9,13,24,25 and decrease bone formation.13,26 Furthermore, it has been shown that ROS plays an important role in the formation of osteoclasts by upregulating RANKL.27 Studies of the role of oxidative stress in the mechanism of alveolar bone breakdown are sparse,7,28 and the molecular mechanisms that link oxidative stress and bone resorption are not fully understood.27 The purpose of this study is to investigate the relationship between oxidative stress and bone resorption biomarkers in the pathologic mechanism of periodontal bone resorption in periodontitis. The associations among total oxidant status (TOS), RANKL, and OPG levels and the RANKL/OPG ratios in serum and GCF were investigated in patients with CP and AgP. The data obtained were compared with those from healthy controls, and the relationship between these parameters and clinical periodontal status was investigated.