Calcium Alleviates Fluoride-Induced Bone Damage by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

Wang, Jinming; Yang, Jian; Cheng, Xiaofang; Xiao, Rui; Zhao, Yangfei; Xu, Hui; Zhu, Yaya; Yan, Zipeng; Ommati, Mohammad Mehdi; Manthari, Ram Kumar; Wang, Jundong

doi:10.1021/acs.jafc.9b04295

Cited by 37 publications

(3 citation statements)

References 45 publications

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“…Ca 2+ is an important second messenger, and the precise regulation of Ca 2+ by calcium pumps, calcium channels, and sodium-calcium exchangers maintains the normal physiological activities of cells (Krebs et al 2011 ). Calpain-2 is a Ca 2+ -dependent cysteine protease whose activity and function depend on intracellular Ca 2+ levels (Bano and Ankarcrona 2018 ; Wang et al 2018 , 2019 ). In the present study, LPZ exposure increased the expression of Calpain-2 and Caspase-12 in MC3T3-E1 cells.…”

Section: Discussionmentioning

confidence: 99%

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

Cheng

Sun

et al. 2022

Mol Med

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Background Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts. Methods A lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin–Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting. Results After 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability. Conclusions Longterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca2+]i) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.

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Section: Discussionmentioning

confidence: 99%

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

Cheng

Sun

et al. 2022

Mol Med

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“…External stimulation led to the accumulation of ROS as well as the imbalance between oxidation and antioxidant system, which cause oxidative stress and cell damage 13–15 . For example, SELENOK‐deficiency could lead to large accumulation of ROS, causing liver damage in chickens 16 .…”

Section: Introductionmentioning

confidence: 99%

Melatonin alleviates 3,3′,4,4′,5‐pentachlorobenzene induced colon injury by relieving oxidative stress

Zhang,

Li,

Xia

et al. 2023

Environmental Toxicology

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Abstract3,3′,4,4′,5‐pentachlorobiphenyl (PCB126) is widely distributed, non‐degradable and bioaccumulative, which can affect the function of tissues and organs of the living organisms. Melatonin (MT) is a sort of indole neurohormone that is mainly secreted by the pineal gland. Numerous studies have shown that MT can alleviate intestinal injury through various mechanisms such as antioxidant, anti‐inflammatory, and anti‐apoptosis. For the above reasons, the aim of this study is to explore the mechanism of intestinal injury in mice after exposure to PCB126 as well as the antagonistic effect of MT. Mice were respectively fed PCB126 (0.326 mg/kg) and/or MT (10 mg/kg) in vivo. In vitro, colonic epithelial cells (MCEC) were treated with PCB126 (150 μM) and/or MT (2 mM). We found that the microscopic structure of colon tissue was impaired after exposure to PCB126. The levels of oxidative stress, the protein and mRNA levels of expression of inflammatory related factors were significantly increased and the expression levels of intestinal tight junction protein were decreased. Notably, MT can promote Nrf2/HO‐1 expression level and reduce the colonic injury caused by PCB126. Further in vitro treatment with reactive oxygen species inhibitors (NAC) showed that it significantly alleviated PCB126‐induced in MCEC cell damage. In summary, the above results suggested that MT alleviates PCB126‐induced colon inflammation by inhibiting the overproduction of reactive oxygen species (ROS) and up‐regulating the expression level of intestinal tight junction protein. Our results contribute to the further comprehension of the intestinal toxicity effects of PCB126 and the significant role of MT in preserving the mechanisms of intestinal injury.

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“…Endemic fluorosis is a global disease ( Wei et al, 2019 ). While physiological doses of fluoride are beneficial to the human body and can promote bone growth and development, excessive fluoride intake leads to its accumulation in a variety of organs, eventually causing fluorosis ( Wang et al, 2019a ). The main symptoms of the disease are only fragments of the damage, however.…”

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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Calcium Alleviates Fluoride-Induced Bone Damage by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

Cited by 37 publications

References 45 publications

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

Melatonin alleviates 3,3′,4,4′,5‐pentachlorobenzene induced colon injury by relieving oxidative stress

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

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