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Diclofenac sodium inhibits NFkappaB transcription in osteoclasts

A Karakawa1, Y Fukawa, M Okazaki

  • 1Department of Pharmacology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. a-karakawa@dent.showa-u.ac.jp

Journal of Dental Research
|October 16, 2009
PubMed

Insights

Diclofenac, an anti-inflammatory drug, inhibits bone remodeling by preventing osteoclast activation. This occurs through blocking the nuclear translocation of phosphorylated nuclear factor kappa B (NFκB), a key regulator of bone cells.

Area of Science:

  • Pharmacology
  • Bone Biology
  • Cellular Signaling

Background:

  • Diclofenac is a widely used non-steroidal anti-inflammatory drug (NSAID).
  • Concerns exist regarding diclofenac's negative impact on bone remodeling.
  • The precise mechanisms underlying diclofenac's effects on bone are not fully understood.

Purpose of the Study:

  • To investigate the inhibitory mechanisms of diclofenac on osteoclast differentiation and activation.
  • To explore the role of nuclear factor kappa B (NFκB) signaling in diclofenac's effects on bone remodeling.

Main Methods:

  • Osteoclasts were differentiated from mouse hematopoietic stem cells and treated with diclofenac.
  • Assays included tartrateresistant acid phosphatase staining, pit formation assays, and cathepsin K transcript analysis.
  • Western blotting was used to assess the translocation of NFκB and its inhibitor (IκB).

Main Results:

  • Diclofenac reduced the number of osteoclasts and inhibited their bone resorption activity in a dose-dependent manner.
  • Cathepsin K expression, a marker of osteoclast activity, was significantly downregulated by diclofenac over time.
  • Diclofenac treatment led to increased cytosolic IκB accumulation, suppressing the nuclear translocation of phosphorylated NFκB.

Conclusions:

  • Diclofenac inhibits osteoclast differentiation and activation, thereby negatively impacting bone remodeling.
  • The mechanism involves the suppression of phosphorylated NFκB nuclear translocation.
  • This study elucidates a novel pathway through which diclofenac affects bone metabolism.

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