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Effects of different Ca2+ level on fluoride-induced apoptosis pathway of endoplasmic reticulum in the rabbit osteoblast in vitro
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2018-04-08
Jinming Wang, Yangfei Zhao, Xiaofang Cheng, Yanyan Li, Huimiao Xu, Ram Kumar Manthari, Jundong Wang

In reviewing the literature, the cellular mechanism of fluoride F-induced osteoblast OB cells apoptosis is diverse and perplexing, but detailed regulatory pathway, targets and role of extracellular Ca2+ remains still unclear. Hence, in the present study, we investigated the effects of F (9 mg/L F ion) and different Ca2+ (0.5, 1, 2, 4, 8 mmol/L) levels treatment on the proliferation rate of osteoblast cells, intracellular free Ca2+ ([Ca2+]i) and endoplasmic reticulum (ER) stress apoptosis pathway related gene levels of rabbit OB cells. Our results demonstrated that F exposure had a pronounced negative effect on osteoblast survival, further different Ca2+ levels treatment suggested that low concentration of Ca2+ (0.5–1 mmol/L) relieved the damaged effect, on the contrary, high concentration of Ca2+ (2–8 mmol/L) enhanced the effect. In addition, F significantly increased [Ca2+]i levels and the expression of ER stress-induced cell apoptosis pathway related genes. Treatment with 0.5–1 mmol/L Ca2+ markedly reversed the F-induced harmful effects, but high dose Ca2+ (2–8 mmol/L) enhanced these effects. In summary, 0.5–1 mmol/L Ca2+ can alleviate F-induced OB cells injure through ER stress apoptosis pathway, which provided a dose basis for the future study on the treatment of skeletal fluorosis with Ca2+.



中文翻译:

不同钙对2+对兔成骨细胞的内质网的氟化物诱导的细胞凋亡途径的水平在体外

在回顾文献中,氟化物F诱导的成骨OB细胞凋亡的细胞机制是多种多样的和令人困惑的,但细胞外Ca 2+的详细调节途径,靶标和作用仍不清楚。因此,在本研究中,我们研究了F(9 mg / LF离子)和不同Ca 2+(0.5、1、2、4、8 mmol / L)处理对成骨细胞,细胞内增殖速率的影响。游离Ca 2+(内[Ca 2+ ] i)和兔OB细胞的内质网(ER)应力凋亡途径相关基因的水平。我们的结果表明F暴露对成骨细胞的存活有明显的负面影响,进一步不同的Ca 2+水平处理表明低浓度的Ca2+(0.5-1 mmol / L)减轻了损伤的作用,相反,高浓度的Ca 2+(2-8 mmol / L)增强了作用。此外,F显着增加了[Ca 2+ ] i水平和内质网应激诱导的细胞凋亡途径相关基因的表达。用0.5–1 mmol / L Ca 2+处理可明显逆转F诱导的有害作用,但高剂量Ca 2+(2–8 mmol / L)可增强这些作用。综上所述,0.5-1 mmol / L Ca 2+可以通过内质网应激凋亡途径减轻F诱导的OB细胞损伤,为进一步研究Ca 2+治疗骨骼氟症提供了剂量依据。

更新日期:2018-04-08
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