Effects of Fluoride on the Expression of Beclin1 and mTOR in Ameloblasts

Lei, Shuang; Zhang, Ying; Kaiqiang, Zhang; Li, Jian; Liu, Lu

doi:10.1159/000441052

Cited by 16 publications

(24 citation statements)

References 36 publications

(28 reference statements)

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“…Recently, it was demonstrated that uoride also induces autophagy due to an increased expression of Beclin1 and LC3 and a decreased expression of p62 in osteoblasts [17,45]. Similarly, a dose-response pattern in LC3-II protein expression in ameloblastderived cells has been observed with uoride treatment [30], which decreases after increasing the concentration of uoride. The present study demonstrated that NaF treated groups had increased mRNA and protein expression levels of p62 and suppressed levels of Beclin1 (Fig.…”

Section: Discussionmentioning

confidence: 91%

“…This further indicates that periodontal cells are less sensitive to autophagy. Lei et al demonstrated that high uoride could cause autophagy of HAT-7 cells, especially related to the expression of Beclin1 [30]. It has also been postulated that the regulation of p62 is responsible for controlling the formation of intracellular inclusion bodies in autophagy, and Beclin1 is involved in the initial steps of the formation of autophagosomes.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, it has been observed that autophagy in osteoblasts can be modulated by uoride. It is also quite possible that uoride may in uence autophagy in stem cells from apical papillas and their differentiation [30].…”

Section: Introductionmentioning

confidence: 99%

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Oral toxicity to high level sodium fluoride causes impairment of autophagy

Oka

Zhang

et al. 2020

Preprint

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Background: Gingival recession and concomitant alveolar bone resorption are hallmarks of periodontal diseases and excessive fluoride intake has some deleterious effects on teeth, bone and soft tissues. Autophagy is a highly conserved intracellular digestion process that degrades damaged proteins and organelles but the biological roles of autophagy in pathological aspects of oral tissues remain largely unknown. We sought to elucidate the function of autophagy, especially its interplay with apoptosis and oxidative stress, in the oral toxicity induced by exposure to 5 mM sodium fluoride (NaF). Methods: HCEM2 cementoblast cells in culture were exposed to 5 mM NaF for 5 min, after which cell viability and cell apoptosis were assessed using the MTS assay and an Annexin V-FITC/PI apoptosis detection kit, respectively. Real-time quantitative RT-PCR and Western blotting were performed to characterize the mRNA and protein expression levels of markers for autophagy, apoptosis, and oxidative stress. C57BL/6 mice were exposed to 5 mM NaF in their drinking water from 12 to 58 weeks. Micro-computed tomography was used to measure changes in their alveolar bone while immunohistochemistry and immunofluorescence staining was used to evaluate protein expression levels of autophagy, apoptosis, and oxidative stress markers.Results: Cementoblasts exposed to 5 mM NaF had decreased levels of autophagy, as shown by reduced expression levels of ATG5, Beclin1 and LC3-II, elicited excessive apoptosis, which in turn induced oxidative stress and inflammation, as manifested by elevated levels of Bax, cleaved caspase-3, SOD1 and phospho NF-κB. Consistently, the in vivo results verified the findings of the in vitro study and treatment of mice with 5 mM NaF resulted in histological abnormalities in periodontal tissues, induced excessive oxidative stress and apoptosis, and reduced autophagy. These results correlated with the immunofluorescence observations, thus confirming the pivotal role of autophagic flux dysfunction in 5 mM NaF-induced cell death. Micro-computed tomography analysis demonstrated that 5 mM NaF caused a decrease in bone areas of mice compared with controls. Exposure to 5 mM NaF induced RANKL (receptor activator of nuclear factor κB ligand) and cathepsin K expression in periodontal tissues, while ATG5 and Beclin1 expression was abrogated by 5 mM NaF.Conclusion: Taken together, our findings suggest that 5 mM NaF elicits oral toxicity that contributes to excessive apoptosis, oxidative stress, and defective autophagy, which aggravates periodontal tissue damage.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Oral toxicity to high level sodium fluoride causes impairment of autophagy

Oka

Zhang

et al. 2020

Preprint

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“…Expression of beclin1, which is required for autophagosome formation, decreases the expression of mTOR increased at 1.2 mmol/l NaF (25). Fluoride promoted cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX) as far as DNA damage and cell death (18).…”

Section: In Vitro Studiesmentioning

confidence: 98%

Fluoride Induces Apoptosis in Mammalian Cells: In Vitro and In Vivo Studies

Ribeiro

Cardoso

Yujra

et al. 2017

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Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

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“…Estas dos últimas, marcadores de los ameloblastos en la etapa de maduración (Kawano et al 2002). Estas células también han sido usadas con el propósito de conocer el papel de la autofagia en la fluorosis dental y sus mecanismos de acción (Lei et al 2015). Sin embargo, se requieren más estudios para determinar si las células epiteliales de rata pueden servir como un modelo optimo que permita conocer los roles fisiopatológicos de los ameloblastos a lo largo de su proceso de diferenciación y el papel de factores que modifiquen una adecuada formación del esmalte dental.…”

Section: Impacto Da Concentração De Soro Bovino Fetal Nas Células Epiunclassified

Impacto de la concentración de suero fetal bovino sobre las células epiteliales dentales

Simancas-Escorcia

Caballero

2019

entramado

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El esmalte dental, tejido más duro del cuerpo humano, es formado por medio de la diferenciación de células epiteliales conocidas como ameloblastos. Recientemente, las células epiteliales dentales de incisivo de rata han sido utilizadas como modelo celular de eventos fisiopatológicos durante la formación del esmalte dental. Sin embargo, en función de los eventos estudiados es meritorio comprender su comportamiento, particularmente cuando la concentración del Suero Fetal Bovino (SFB) varia. El propósito de este trabajo es evaluar el impacto de la concentración del SFB sobre el crecimiento, proliferación y supervivencia de las células epiteliales dentales. Células epiteliales dentales fueron cultivadas en DMEM/F12, en presencia y ausencia de SFB. Observaciones morfológicas e inmunohistoquímicos de la actina, vimentina y fibronectina fueron realizados. Los resultados permitieron constatar que la ausencia de SFB afectó negativamente la proliferación de las células epiteliales dentales, pero mantuvo una expresión optima de la actina y vimentina. Se identificó una alteración en la expresión de la fibronectina en las células tratadas en ausencia de SFB. En conclusión, la carencia de SFB disminuyo drásticamente la supervivencia, proliferación y expresión de la fibronectina en las células epiteliales dentales de rata.

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Effects of Fluoride on the Expression of Beclin1 and mTOR in Ameloblasts

Cited by 16 publications

References 36 publications

Oral toxicity to high level sodium fluoride causes impairment of autophagy

Oral toxicity to high level sodium fluoride causes impairment of autophagy

Fluoride Induces Apoptosis in Mammalian Cells: In Vitro and In Vivo Studies

Impacto de la concentración de suero fetal bovino sobre las células epiteliales dentales

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