Biological Trace Element Research

, Volume 162, Issue 1–3, pp 219–226 | Cite as

Fluoride Affects Calcium Homeostasis and Osteogenic Transcription Factor Expressions Through L-type Calcium Channels in Osteoblast Cell Line

  • Xiao-qin Duan
  • Zhi-tao Zhao
  • Xiu-yun Zhang
  • Ying Wang
  • Huan Wang
  • Da-wei Liu
  • Guang-sheng Li
  • Ling JingEmail author


Osteoblast L-type voltage-dependent calcium channels (VDCC) play important roles in maintaining intracellular homeostasis and influencing multiple cellular processes. In particular, they contribute to the activities and functions of osteoblasts (OBs). In order to study how L-type VDCC modulate calcium ion (Ca2+) homeostasis and the expression of osteogenic transcription factors in OBs exposed to fluoride, MC3T3-E1 cells were exposed to a gradient of concentrations of fluoride (0, 2.0, 5.0, 10.0 mg/L) in combination with 10 μM nifedipine, a specific inhibitor of VDCC, for 48 h. We examined messenger RNA (mRNA) and protein levels of Cav1.2, the main subunit of VDCC, and c-fos, c-jun, runt-related transcription factor 2 (Runx2), osterix (OSX), and intracellular free Ca2+ ([Ca2+]i) concentrations in MC3T3-E1 cells. Our results showed that [Ca2+]i levels increased in a dose-dependent manner with increase in concentration of fluoride. Meantime, results indicated that lower concentrations of fluoride (less than 5 mg/L, especially 2 mg/L) can lead to high expression of Cav1.2 and enhance osteogenic function, while high concentration of fluoride (10 mg/L) can induce decreased Cav1.2 and osteogenic transcriptional factors in MC3T3E1 cells exposed to fluoride. However, the levels of [Ca2+]i, Cav1.2, c-fos, c-jun, Runx2, and OSX induced by fluoride were significantly altered and even reversed in the presence of nifedipine. These results demonstrate that L-type calcium channels play a crucial role in Ca2+ homeostasis and they affect the expression of osteogenic transcription factors in fluoride-treated osteoblasts.


Osteoblast (OB) Fluoride L-type voltage-dependent calcium channels (VDCC) Cav1.2 Nifedipine 



This work was supported by a grant for skeletal fluorosis research from the National Natural Science Foundation of China (81172608).

Conflict of Interest

All authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Xiao-qin Duan
    • 1
  • Zhi-tao Zhao
    • 2
  • Xiu-yun Zhang
    • 2
  • Ying Wang
    • 3
  • Huan Wang
    • 1
  • Da-wei Liu
    • 2
  • Guang-sheng Li
    • 2
  • Ling Jing
    • 2
    Email author
  1. 1.Department of Rehabilitation Medicine of the Second Hospital Norman BethuneJiLin UniversityChangchunPeople’s Republic of China
  2. 2.Institute of Endemic DiseaseJilin UniversityChangchunPeople’s Republic of China
  3. 3.The First Hospital Norman BethuneJiLin UniversityChangchunPeople’s Republic of China

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