Diclofenac Sodium Inhibits NFκB Transcription in Osteoclasts

A non-steroidal anti-inflammatory drug, diclofenac, acts efficiently against inflammation; however, down-regulation of diclofenac on bone remodeling has raised concerns. The inhibitory mechanisms of diclofenac are poorly understood. We hypothesized that diclofenac down-regulates osteoclast differentiation and activation via inhibition of the translocation of phosphorylated nuclear factor kappa B (NF kappa B). When osteoclasts prepared from mouse hematopoietic stem cells were treated with diclofenac, tartrate-resistant acid phosphatase-positive multinucleated cells decreased in a concentration-dependent manner. Pit formation assay revealed the abolition of osteoclastic bone resorption; levels of cathepsin K transcripts, an osteoclastic resorption marker, were down-regulated time-dependently. Diclofenac induced the accumulation of the inhibitor of kappa B in cytosol, which led to suppression of the nuclear translocation of NF kappa B and phosphorylated NF kappa B. These results suggest that the novel mechanism of diclofenac for bone remodeling is associated with phosphorylated NF kappa B reduction, which regulates osteoclast differentiation and activation.