Sodium fluoride induces apoptosis and autophagy via the endoplasmic reticulum stress pathway in MC3T3-E1 osteoblastic cells
Fluorosis and bone pathologies can be caused by chronic and/or excessive fluoride intake. Despite this, few studies have been conducted on the cellular mechanisms underlying osteoblast toxicity in the presence of NaF. Here, we investigated the effects of fluoride on MC3T3-E1 cells. We showed that the proliferation of MC3T3-E1 cells was inhibited by exposure to NaF. In addition, apoptosis was induced by NaF, as caspase-associated proteins showed a higher level of expression and apoptotic bodies were formed. Furthermore, endoplasmic reticulum (ER) stress induced by NaF activated the unfolded protein response (UPR) and upregulated the expression of the glucose-regulated proteins 94 (GRP94) and 78 (BiP). Therefore, ER stress plays a vital role in NaF-induced autophagy and apoptosis. Furthermore, apoptosis is promoted following the inhibition of NaF-induced autophagy. In conclusion, under NaF treatment, the ER stress-signaling pathway is activated, leading to apoptosis and autophagy and affecting the proliferation and survival of MC3T3-E1 cells.
KeywordsSodium fluoride Apoptosis Autophagy ER stress Osteoblastic cells
The authors gratefully acknowledge funding support from the National Natural Science Foundation of China (Grant No. 81670956) and Shanghai Cooperative International Project (Grant No.16520710400) of Shanghai Committee of Science and Technology, China.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
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