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Journal of Dental Research
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Biological

IL-1{alpha} Stimulates Cathepsin K Expression in Osteoclasts via the Tyrosine Kinase-NF-{kappa}B Pathway

S. Kamolmatyakul1, W. Chen1,2, S. Yang1,2, Y. Abe1, R. Moroi1, A.M. Ashique1,2 and Y.-P. Li1,2,*

1 Department of Cytokine Biology, The Forsyth Institute, 140 The Fenway, Boston, MA 02115, USA; and 2 Harvard-Forsyth Department of Oral Biology, The Forsyth Institute & Harvard School of Dental Medicine, Boston, MA 02115, USA;

Correspondence: * corresponding author, ypli{at}forsyth.org

Interleukin-1{alpha} (IL-1{alpha}) is a powerful activator of osteoclast cells. However, the underlying mechanism for this activation is unknown. In this study, we reveal that IL-1{alpha} 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-{kappa}B, or Genistein, a protein tyrosine kinase inhibitor, suggesting that IL-1{alpha} up-regulation may be via the tyrosine kinase-NF-{kappa}B pathway to regulate cathepsin K expression. Antisense oligonucleotides to p65, but not the p50 subunit of NF-{kappa}B, suppress the IL-1{alpha}-induced expression of cathepsin K. We therefore conclude that IL-1{alpha} up-regulates cathepsin K gene expression at the transcription level, and this regulation may be via the tyrosine-kinase-NF-{kappa}B pathway.

Key Words: interleukin-1alpha • cathepsin K • osteoclast • NF-{kappa}B • tyrosine kinase

Journal of Dental Research, Vol. 83, No. 10, 791-796 (2004)
DOI: 10.1177/154405910408301011


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