Proteomic analysis of infected root canals with apical periodontitis in patients with type 2 diabetes mellitus: A cross‐sectional study

Abstract

Aim This study aimed to quantitatively and qualitatively determine the proteomic profile of apical periodontitis (AP) in type 2 diabetes mellitus (T2DM) patients in comparison with systemically noncompromised patients and to correlate the protein expression of both groups with their biological functions. Methodology The sample consisted of 18 patients with asymptomatic AP divided into two groups according to the presence of T2DM: diabetic group—patients with T2DM (n = 9) and control group—systemically healthy patients (n = 9). After sample collection, the root canal samples were prepared for proteomic analysis using reverse‐phase liquid chromatography‐mass spectrometry. Label‐free quantitative proteomic analysis was performed by Protein Lynx Global Service software. Differences in protein expression between groups were calculated using t‐test (p < .05). Biological functions were analysed using the Homo sapiens UniProt database. Results A total of 727 human proteins were identified in all samples. Among them, 124 proteins common to both groups were quantified, out of which 65 proteins from the diabetic group showed significant differences compared with the control: 43 upregulated (p < .05) and 22 downregulated (p < .05) proteins. No significant differences in protein expression were seen for the remaining 59 proteins (p > .05). Most proteins with differences in expression were related to immune/inflammatory response. Neutrophil gelatinase‐associated lipocalin, Plastin‐2, Lactotransferrin and 13 isoforms of immunoglobulins were upregulated. In contrast, Protein S100‐A8, Protein S100‐A9, Histone H2B, Neutrophil defensin 1, Neutrophil defensin 3 and Prolactin‐inducible protein were downregulated. Conclusions Quantitative differences were demonstrated in the expression of proteins common to diabetic and control groups, mainly related to immune response, oxidative stress, apoptosis and proteolysis. These findings revealed biological pathways that provide the basis to support clinical findings on the relationship between AP and T2DM.

The role of pathogens in diabetes pathogenesis and the potential of immunoproteomics as a diagnostic and prognostic tool

“…Salivary proteomics of diabetic patients identified TXNDC17, ZG16B, and FAM3D as novel biomarkers of hyperglycemia and oral disease in DM2 patients with poor glycemic control ( Jia et al, 2021 ). An MS-DIA based proteomic analysis of infected root canals of DM2 patients identified fortythree overexpressed proteins, the majority of which were related to immune-inflammatory response ( Loureiro et al, 2022 ). Withatanung et al (2019) performed proteomics of Burkholderia pseudomallei infected Neutrophils isolated from DM2 patients observing elevated levels of pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNFα as well as enhanced apoptosis.…”

Participação da atividade redox e das armadilhas extracelulares de neutrófilos na gênese e desenvolvimento da lesão periapical induzida experimentalmente em camundongos

“…Porém, em níveis elevados, possuem efeitos deletérios que promovem a morte celular pulpar ou necrose desse tecido (Duncan e Cooper, 2020;Gallorini et al, 2021;. Alguns estudos mostraram a participação do stress oxidativo no desenvolvimento de lesões periapicais (Inchingolo et al, 2013;Hernández-Ríos et al, 2017;Jakovljevic et al, 2018;Loureiro et al, 2021;Zivanovic et al, 2021;Loureiro et al, 2022), estando associado à dor e reabsorção óssea (Vengerfeldt et al, 2017). Nesse contexto, um estudo demonstrou a ação promissora do medicamento dioscina, de ação antioxidante, no controle da periodontite apical refratária, uma vez que estimulou, in vivo, a osteogênese de pré-osteoblastos por meio da inibição das ROS (Yin et al, 2020).…”

“…Nesse contexto, um estudo demonstrou a ação promissora do medicamento dioscina, de ação antioxidante, no controle da periodontite apical refratária, uma vez que estimulou, in vivo, a osteogênese de pré-osteoblastos por meio da inibição das ROS (Yin et al, 2020). Adicionalmente, um estudo recente demonstrou, por meio de análise proteômica, menores níveis de proteínas relacionadas ao stress oxidativo em abscessos apicais agudos em comparação a amostras de dentes com periodontite apical crônica (Loureiro et al, 2022).…”

“…Outro trabalho demonstrou, ainda, que as lesões pulpares associadas ao diabetes poderiam ter como causa o dano oxidativo mitocondrial . Nesse contexto, recentemente Loureiro et al (2022) avaliaram a expressão de proteínas em amostras do canal radicular de dentes com periodontite apical assintomática, de pacientes com diabetes tipo 2 e de pacientes não comprometidos sistemicamente. Esses autores puderam evidenciar que, embora as proteínas relacionadas ao stress oxidativo, como a MPO, peroxiredoxinas, eosinófilo peroxidase e gliceraldeído-3-fosfato desidrogenase foram observadas em ambos os grupos, estas estiveram maior expressão nos pacientes diabéticos.…”

“…Alguns estudos mostraram a participação do stress oxidativo no desenvolvimento de lesões periapicais (Inchingolo et al, 2013;Hernández-Ríos et al, 2017;Jakovljevic et al, 2018;Loureiro et al, 2021;Zivanovic et al, 2021;Loureiro et al, 2022), estando associado à dor e reabsorção óssea (Vengerfeldt et al, 2017). Adicionalmente, um estudo recente demonstrou, por meio de análise proteômica, menores níveis de proteínas relacionadas ao stress oxidativo em abscessos apicais agudos em comparação a amostras de dentes com periodontite apical crônica (Loureiro et al, 2022).…”