ABSTRACT
Abstract Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. Objective: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. Methodology: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. Results: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1β (IL-1β) and IL-6 protein expression. Conclusions: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.
Subject(s)
Animals , Male , Periodontitis/metabolism , Periodontitis/drug therapy , Calcitriol/pharmacology , NF-kappa B/drug effects , Bone Density Conservation Agents/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Periodontitis/pathology , Reference Values , Calcitriol/analysis , Immunohistochemistry , Blotting, Western , Reproducibility of Results , Alveolar Bone Loss , NF-kappa B/analysis , Interleukin-6/analysis , Treatment Outcome , Receptors, Aryl Hydrocarbon/analysis , Receptors, Aryl Hydrocarbon/drug effects , Porphyromonas gingivalis , Caspase 1/analysis , Bone Density Conservation Agents/analysis , Interleukin-1beta/analysis , NLR Family, Pyrin Domain-Containing 3 Protein/analysis , Gingiva/drug effects , Gingiva/metabolism , Gingiva/pathology , Mice, Inbred C57BLABSTRACT
Doenças cardiovasculares são frequentes no curso da insuficiência renal crônica, constituem importante causa de óbito, e causam 1/3 das hospitalizações de doentes dialíticos. Hiperparatireoidismo secundárioé o distúrbio metabólico mais comum na insuficiência renal, cuja fisiopatologia envolve alterações no equilíbriodo cálcio, fósforo, calcitriol e paratormônio. Objetivo: Avaliar a prevalência de alterações ecocardiográficas em pacientes renais crônicos com hiperparatireoidismo secundário, de acordo com níveis plasmáticos de paratormônio.Métodos: Estudo retrospectivo, realizado com base em dados registrados em prontuários entre 2005 e 2007,incluindo 52 indivíduos de ambos os sexos, com doença renal crônica em programa regular de diálise, estratificados com base nos níveis plasmáticos de paratormônio em três grupos: Grupo I ≤ 299pg/mL (n=10); Grupo II entre 300-499 pg/mL (n=21); e Grupo III ≥500 pg/mL (n=21). Foram avaliados os seguintes parâmetros ecocardiográficos: diâmetros da raiz da aorta, do átrio esquerdo e dos ventrículos; espessuras do septo e da parede posterior; fração de ejeção; e volumes diastólico e sistólico finais.Resultados: A análise comparativa dos achados ecocardiográficos nos três grupos revelou que a única variávelque apresentou significância estatística (p 0,009) foi a espessura diastólica da parede posterior. Conclusão: Doentes renais crônicos com hiperparatireoidismo secundário podem apresentar alteraçõesecocardiográficas, algumas das quais apresentam correlação com níveis circulantes de paratormônio....
Background: Cardiovascular diseases are frequent in the course of chronic kidney disease, are an important cause of death, and cause 1/3 of hospitalizations of patients on dialysis. Secondary hyperparathyroidism is the most common metabolic disorder in kidney failure. Its pathophysiology involves changes in the balance of calcium, phosphorus, calcitriol and parathyroid hormone. Objective: To assess the prevalence of echocardiographic abnormalities in chronic kidney disease patients with secondaryhyperparathyroidism, according to plasma levels of parathyroid hormone.Methods: Retrospective study conducted based on data recorded in medical records between 2005 and 2007, including 52 individuals of both sexes with chronic kidney disease on a regular dialysis program, stratified based on plasma levels of parathyroid hormoneinto three groups: Group I ≤ 299pg/mL (n=10); Group II between 300-499 pg/mL (n=21); and Group III ≥500 pg/mL (n=21).We evaluated the following echocardiographic parameters: aortic root diameter, left atrial and ventricular diameter; septal and posteriorwall thickness; ejection fraction; and end diastolic and systolic volumes. Results: The comparative analysis of the echocardiographic findings in the three groups revealed that the only variable presenting statistical significance (p 0.009) was diastolic posterior wall thickness. Conclusion: Patients with chronic kidney disease with secondary hyperparathyroidism may present echocardiographic changes, some of which correlate with circulating levels of parathyroid hormone...
Subject(s)
Humans , Male , Female , Middle Aged , Echocardiography/methods , Hyperparathyroidism, Secondary/complications , Hyperparathyroidism, Secondary/physiopathology , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/mortality , Patients , Chronic Disease , Calcium/analysis , Calcitriol/analysis , Renal Dialysis/methods , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnosis , Phosphorus/analysis , Prevalence , Retrospective Studies , Risk Factors , Kidney/physiopathology , Data Interpretation, StatisticalABSTRACT
O hiperparatiroidismo secundário (HPTS), observado nos doentes urémicos, apesar de se instalar desde estadios precoces da insuficiência renal,apresenta manifestações clínicas pouco específicas e frequentemente tardias. Para além da promissora técnica de avaliação da arquitectura trabecularóssea por tomografia quantitativa microcomputorizada os métodos imagiológicos são de escassa utilidade no diagnóstico das alterações ósseasassociadas ao HPTS. Ao longo dos últimos anos foram avaliados diversos marcadores bioquímicos da remodelação óssea e a respectiva utilidade nodiagnóstico não invasivo da osteodistrofia renal. Finalmente, é ainda discutido o eventual papel de factores locais (citoquinas e factores de crescimento) na modulação da remodelação óssea.
Secondary hyperparathyroidism represents one extreme of the spectrum of the bone and endocrine changes observed in uraemic patients, and may develop since early stages of renal failure. The clinical symptoms and signs are non-specific and the contribution of image evaluation in the diagnosis of secondary hyperparathyroidism is, frequently, misleading. In this review, in addition to the classic modulators of bone remodeling, like parathyroid hormone (and PTHfragments), calcitriol and calcitonin, the role of others local factors involved in osteoblast and osteoclast activation, like cytokines and growth factors, is alsodiscussed.