Tumor necrosis factor-α induces interleukin-34 expression through nuclear factor‑κB activation in MC3T3-E1 osteoblastic cells

Mol Med Rep. 2014 Sep;10(3):1371-6. doi: 10.3892/mmr.2014.2353. Epub 2014 Jun 25.


Osteoblasts produce various types of cytokines under pathological conditions and control osteoclast differentiation. Tumor necrosis factor-α (TNF-α) has been demonstrated to exert complex effects in osteoblasts under local inflammatory conditions, including in periodontal and periapical diseases. Interleukin-34 (IL-34) has been recently identified as a novel regulatory factor for the differentiation and function of osteoclasts. The present study provides the first evidence, to the best of our knowledge, that the expression of IL-34 is induced by TNF-α through nuclear factor-κB (NF-κB) activation in MC3T3-E1 osteoblastic cells. TNF-α induced IL-34 expression in a dose- and time-dependent manner. Immunocytochemistry with an NF-κB antibody demonstrated that NF-κB was mainly localized in the cytoplasm of the untreated MC3T3-E1 cells. Rapid translocation of NF-κB from the cytoplasm to the nucleus was observed in the cells treated with TNF-α for 15 min. Translocation and transcriptional activity of NF-κB were also determined by western blotting and a luciferase reporter assay, respectively. Pretreatment with 100 µM CAPE, an inhibitor of NF-κB, significantly inhibited TNF-α-induced IL-34 expression. These results indicate that TNF-α induces IL-34 expression via NF-κB in osteoblasts.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Differentiation / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Dose-Response Relationship, Drug
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Interleukins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • interleukin-34, mouse