Effects of different Ca2+ level on fluoride-induced apoptosis pathway of endoplasmic reticulum in the rabbit osteoblast in vitro

Abstract

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⁺.

Keywords: Apoptosis; Calcium; Endoplasmic reticulum; Fluoride; Osteoblast.