IL-1α Stimulates Cathepsin K Expression in Osteoclasts via the Tyrosine Kinase-NF-κB Pathway

Abstract

Interleukin-1α (IL-1α) is a powerful activator of osteoclast cells. However, the underlying mechanism for this activation is unknown. In this study, we reveal that IL-1α up-regulates the expression of cathepsin K protein, a key protease in bone resorption, by five-fold. Northern blot analysis and promoter analysis show that this induction occurs at the transcriptional level, in a dose-responsive and time-dependent manner. No increase in expression occurs in the presence of either pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-κB, or Genistein, a protein tyrosine kinase inhibitor, suggesting that IL-1α up-regulation may be via the tyrosine kinase-NF-κB pathway to regulate cathepsin K expression. Antisense oligonucleotides to p65, but not the p50 subunit of NF-κB, suppress the IL-1α-induced expression of cathepsin K. We therefore conclude that IL-1α up-regulates cathepsin K gene expression at the transcription level, and this regulation may be via the tyrosine-kinase-NF-κB pathway.