Impact of fluoride exposure at different concentrations on preosteoblastic cells: Molecular, biochemical, and morphological insights

Abstract

Fluoride can harm various tissues depending on its concentration and exposure duration. While its effects on mineralized tissues like bones and teeth are known, few studies have explored its impact on preosteoblastic cells. This study examined the effects of fluoride on differentiating osteoblastic cells. M3CT3-E1 preosteoblastic cells were cultured for 24 h or 3, 5, or 7 days with fluoride concentrations of 1, 10, or 100 μg/mL. Cell viability, oxidative stress biomarkers, mitochondrial membrane potential, cell cycle distribution, apoptosis, and morphology were assessed. After statistical analysis, At 100 μg/mL, fluoride modulated cell viability in a dose- and time-dependent manner, increasing reactive oxygen species levels and lipid peroxidation (1.382 ± 0.163 vs. 0.826 ± 0.081; p = 0.0125). Oxidative stress markers such as superoxide dismutase (SOD) (4.008 ± 0.425 vs. 0.724 ± 0.474; p = 0.0025) and glutathione (GSH) (78.38 ± 4.506 vs. 45.65 ± 2.900; p = 0.0003) were also elevated. High fluoride concentrations impaired mitochondrial activity and disrupted the cell cycle, affecting the G0/G1, S, and G2/M phases. These changes caused irreversible damage, including apoptosis and alterations in cell morphology. High fluoride concentrations can significantly damage preosteoblastic cells, reducing viability, altering redox status, impairing mitochondrial function, and disrupting the cell cycle, leading to cell death. These findings underscore that fluoride toxicity is concentration-dependent and reinforce the safety of exposure to doses of fluoride such as those found in the optimally fluoridated water.