Sodium fluoride induces apoptosis and autophagy via the endoplasmic reticulum stress pathway in MC3T3-E1 osteoblastic cells

  • Xueyan Li
  • Li Meng
  • Feng Wang
  • Xiaojie Hu
  • Youcheng Yu


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.


Sodium 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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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of StomatologyEye & Ent Hospital of Fudan UniversityShanghaiChina
  2. 2.Department of PharmacyQingdao Central HospitalQingdaoChina
  3. 3.Department of StomatologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
  4. 4.Plastic and Reconstructive Department, Shanghai 9th People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  5. 5.Department of Stomatology, Zhongshan HospitalFudan UniversityShanghaiChina

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