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NaF activates MAPKs and induces apoptosis in odontoblast-like cells

H Karube1, G Nishitai, K Inageda

  • 1Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Journal of Dental Research
|June 5, 2009
PubMed

Insights

Sodium fluoride (NaF) triggers apoptosis in odontoblast-like cells by activating specific signaling pathways. The c-Jun NH(2)-terminal kinase (JNK) pathway plays a key role in this fluoride-induced cell death.

Area of Science:

  • Cell Biology
  • Toxicology
  • Biochemistry

Background:

  • The precise cytotoxic mechanisms of fluoride on odontoblasts remain incompletely understood.
  • Odontoblasts are crucial for dentin formation and maintaining tooth vitality.

Purpose of the Study:

  • To investigate whether sodium fluoride (NaF) induces apoptosis in MDPC-23 odontoblast-like cells.
  • To elucidate the involvement of mitogen-activated protein kinase (MAPK) signaling pathways in NaF-induced apoptosis.

Main Methods:

  • MDPC-23 cells were treated with 5 mM NaF for 24 hours.
  • Assessed markers of apoptosis including caspase-3 activation, PARP cleavage, DNA fragmentation, and nucleosome release.
  • Investigated the phosphorylation status of various MAPKs (JNK, p38, ERK).
  • Utilized specific inhibitors (SP600125 for JNK, U0126 for ERK) to assess pathway involvement.

Main Results:

  • NaF exposure led to significant caspase-3 activation, PARP cleavage, DNA fragmentation, and increased cytoplasmic nucleosomes.
  • NaF induced a biphasic phosphorylation of ERK and sustained phosphorylation of JNK and p38.
  • Apoptosis was significantly reduced by the JNK inhibitor SP600125 and mildly by the ERK inhibitor U0126.
  • Inhibition of p38 activity did not affect NaF-induced apoptosis.

Conclusions:

  • Sodium fluoride induces apoptosis in odontoblast-like cells.
  • The c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) signaling pathways are involved in NaF-induced apoptosis.
  • JNK plays a more significant role than ERK in mediating fluoride-induced apoptosis in these cells.

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