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IL-1 Stimulates Cathepsin K Expression in Osteoclasts via the Tyrosine Kinase-NF- 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 (IL-1 ) is a powerful activator of osteoclast cells. However, the underlying mechanism for this activation is unknown. In this study, we reveal that IL-1 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- B, or Genistein, a protein tyrosine kinase inhibitor, suggesting that IL-1 up-regulation may be via the tyrosine kinase-NF- B pathway to regulate cathepsin K expression. Antisense oligonucleotides to p65, but not the p50 subunit of NF- B, suppress the IL-1 -induced expression of cathepsin K. We therefore conclude that IL-1 up-regulates cathepsin K gene expression at the transcription level, and this regulation may be via the tyrosine-kinase-NF- B pathway.
Key Words: interleukin-1alpha cathepsin K osteoclast NF- B tyrosine kinase
Journal of Dental Research, Vol. 83, No. 10,
791-796 (2004)
DOI: 10.1177/154405910408301011

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