Calcium relieves fluoride-induced bone damage through the PI3K/AKT pathway

Wang, Jinming; Xu, Hui; Cheng, Xiaofang; Yang, Jian; Yan, Zipeng; Ma, Haili; Zhao, Yangfei; Ommati, Mohammad Mehdi; Manthari, Ram Kumar; Wang, Jundong

doi:10.1039/c9fo02491c

Cited by 25 publications

(17 citation statements)

References 41 publications

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“…In the F+SeII group, SeNPs decreased p-STAT3 protein expression not following the established trend of p-JAK2, which may be related to the more target proteins. Regarding the p-STAT3, although it is an essential downstream substrate of p-JAK2, it can be influenced by the other signaling pathway such as receptor tyrosine kinase (RTK), and the activation of RTK may lead to JAK-independent tyrosine phosphorylation of STAT. , As for the expression levels of JAK2 and STAT3, they showed an opposite trend with corresponding phosphorylated proteins, which was consistent with our previous experimental results of PI3K and AKT . F induced a decrease in the expressions of JAK2 and STAT3 and increased expressions of p-JAK2 and p-STAT3, while SeNPs supplementation inhibited the harmful effects of F on them.…”

Section: Resultssupporting

confidence: 88%

“…57,58 As for the expression levels of JAK2 and STAT3, they showed an opposite trend with corresponding phosphorylated proteins, which was consistent with our previous experimental results of PI3K and AKT. 59 F induced a decrease in the expressions of JAK2 and STAT3 and increased expressions of p-JAK2 and p-STAT3, while SeNPs supplementation inhibited the harmful effects of F on them. Moreover, IL-6 is not only the target gene of p-STAT3 but also the major stimulator of p-STAT3, which is verified by our experimental results, which showed that 0.5 and 1 mg Se/kg BW/day SeNPs reduced the elevation of IL-6 and p-STAT3 in a dose-dependent manner.…”

Section: Protective Effects Of Senps On the Basal Metabolic Index In ...mentioning

confidence: 91%

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Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway

Yang

Hao

et al. 2022

ACS Appl. Mater. Interfaces

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Depression is a mental health problem with typically high levels of distress and dysfunction, and 150 mg/L fluoride (F) can induce depression-like behavior. The development of depression is correlated with neuronal atrophy, insufficient secretion of monoamine neurotransmitters, extreme deviations from the normal microglial activation status, and immune-inflammatory response. Studies found that Se supplementation was related to the improvement of depression. In this study, we applied selenium nanoparticles (SeNPs) for F-induced depression disease mitigation by regulating the histopathology, metabolic index, genes, and protein expression related to the JAK2-STAT3 signaling pathway in vivo. Results showed that F and 2 mg Se/kg BW/day SeNPs lowered the dopamine (DA) content (P < 0.05), altered the microglial morphology, ramification index as well as solidity, and triggered the microglial neuroinflammatory response by increasing the p-STAT3 nuclear translocation (P < 0.01). Furthermore, F reduced the cortical Se content and the number of surviving neurons (P < 0.05), increasing the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 of the cortex (P < 0.01), accompanied by the depression-like behavior. Importantly, 1 mg Se/kg BW/day SeNPs alleviated the microglial ramification index as well as solidity changes and decreased the interleukin-1β secretion induced by F by suppressing the p-STAT3 nuclear translocation (P < 0.01). Likewise, 1 mg Se/kg BW/day SeNPs restored the F-disturbed dopamine and noradrenaline secretion, increased the number of cortical surviving neurons, and reduced the vacuolation area, ultimately suppressing the occurrence of depression-like behavior through inhibiting the JAK2-STAT3 pathway activation. In conclusion, 1 mg Se/kg BW/day SeNPs have mitigation effects on the F-induced depression-like behavior. The mechanism of how SeNPs repair neural functions will benefit depression mitigation. This study also indicates that inhibiting the JAK/STAT pathway can be a promising novel treatment for depressive disorders.

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Section: Resultssupporting

confidence: 88%

Section: Protective Effects Of Senps On the Basal Metabolic Index In ...mentioning

confidence: 91%

Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway

Yang

Hao

et al. 2022

ACS Appl. Mater. Interfaces

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“…The main symptoms of the disease are only fragments of the damage, however. As the study of skeletal fluorosis has been thorough, the deleterious effects of fluoride on bone are well known (Wang et al, 2019b(Wang et al, , 2020. The main performance for osteoblast numbers increases mast cell body, which is the basis for extensive cell damage and apoptosis (Ravanan et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Expression of Autophagy-Related Factors LC3A and Beclin 1 and Apoptosis-Related Factors Bcl-2 and BAX in Osteoblasts Treated With Sodium Fluoride

Deng

Zhang³

et al. 2021

Front. Physiol.

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ObjectiveThis study aims to analyze the expressions of autophagy-related factors light chain 3 alpha (LC3A) and Beclin 1 and apoptosis-related factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (BAX) in primary osteoblasts treated with sodium fluoride (NaF).MethodsOsteoblasts were extracted from Sprague-Dawley rats and treated with 0, 2.5, 5, and 10 mg/L NaF solutions, followed by 10 mmol/L 3-methyladenine (3-MA) for 24 h. The apoptotic rate was determined by flow cytometry, and the expressions of the autophagy- and apoptosis-related factors were measured by western blotting and real-time quantitative polymerase chain reaction.ResultsThe mRNA expressions of LC3A, Beclin 1, and BAX in the NaF-treated osteoblast group were higher than those in the control group, while the protein expressions of these factors in the NaF-treated group were significantly higher than those in the control group. However, the Bcl-2 protein expression in the NaF-treated osteoblasts was significantly decreased compared to that in the control cells. After the 3-MA treatment, the protein expressions of LC3A, Beclin 1, and Bcl-2 were significantly decreased compared with those of the NaF-treated group, whereas the expression of BAX increased. Moreover, the apoptosis rate was increased after the addition of the 3-MA inhibitor.ConclusionNaF stimulation promoted autophagy and apoptosis of the osteoblasts, suggesting the involvement of fluoride damage in these processes.

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“…The binding of FOXO1 acetylation to ATG7 promotes autophagy for cell survival to resist OS [ 23 ]. FOXO1 in the nucleus increases the translation of B-cell lymphoma-2-like protein 1(BIM) to promote apoptosis [ 24 , 25 ]. The levels of ROS affect FOXO cytoplasmic/nuclear shuttling, FOXO stability, and eventually transcription of FOXO-controlled target genes [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

FOXO1 Is a Critical Switch Molecule for Autophagy and Apoptosis of Sow Endometrial Epithelial Cells Caused by Oxidative Stress

Huang

Zhao

et al. 2021

Oxidative Medicine and Cellular Longevity

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Oxidative stress (OS) is involved in various reproductive diseases and can induce autophagy and apoptosis, which determine the different fates of cells. However, the sequence and the switch mechanism between autophagy and apoptosis are unclear. Here, we reported that chronic restraint stress (CRS) induced OS (decreased T-AOC, T-SOD, CAT and GSH-Px and increased MDA) and then disturbed the endocrine environment of sows during early pregnancy, including the hypothalamic-pituitary-ovarian (HPO) and the hypothalamic-pituitary-adrenal (HPA) axes. Meanwhile, after CRS, the KEAP1/NRF2 pathway was inhibited and attenuated the antioxidative ability to cause OS of the endometrium. The norepinephrine (NE) triggered β2-AR to activate the FOXO1/NF-κB pathway, which induced endometrial inflammation. CRS induced the caspase-dependent apoptosis pathway and caused MAP1LC3-II accumulation, SQSTM1/p62 degradation, and autophagosome formation to initiate autophagy. Furthermore, in vitro, a cellular OS model was established by adding hydrogen peroxide into cells. Low OS maintained the viability of endometrial epithelial cells by triggering autophagy, while high OS induced cell death by initiating caspase-dependent apoptosis. Autophagy preceded the occurrence of apoptosis, which depended on the subcellular localization of FOXO1. In the low OS group, FOXO1 was exported from the nucleus to be modified into Ac-FOXO1 and bound to ATG7 in the cytoplasm, which promoted autophagy to protect cells. In the high OS group, FOXO1 located in the nucleus to promote transcription of proapoptotic proteins and then induce apoptosis. Here, FOXO1, as a redox sensor switch, regulated the transformation of cell autophagy and apoptosis. In summary, the posttranslational modification of FOXO1 may become the target of OS treatment.

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Calcium relieves fluoride-induced bone damage through the PI3K/AKT pathway

Abstract: Bone is the main target of fluorosis, and it has been perfectly elaborated that a moderate dosage of calcium (Ca) can alleviate bone fluorosis.

Cited by 25 publications

References 41 publications

Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway

Mitigation Effects of Selenium Nanoparticles on Depression-Like Behavior Induced by Fluoride in Mice via the JAK2-STAT3 Pathway

Expression of Autophagy-Related Factors LC3A and Beclin 1 and Apoptosis-Related Factors Bcl-2 and BAX in Osteoblasts Treated With Sodium Fluoride

FOXO1 Is a Critical Switch Molecule for Autophagy and Apoptosis of Sow Endometrial Epithelial Cells Caused by Oxidative Stress

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