Open AccessIL-1α Stimulates Cathepsin K Expression in Osteoclasts via the Tyrosine Kinase-NF-κB Pathway
Author(s) -
Suttatip Kamolmatyakul,
W. Chen,
Shuo Yang,
Yoshihiro Abe,
Ryoji Moroi,
Amir M. Ashique,
Y.-P. Li
Publication year - 2004
Publication title -
journal of dental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.979
H-Index - 182
eISSN - 1544-0591
pISSN - 0022-0345
DOI - 10.1177/154405910408301011
Subject(s) - cathepsin k , chemistry , nf κb , tyrosine kinase , microbiology and biotechnology , signal transduction , osteoclast , biology , biochemistry , receptor
Interleukin-1alpha (IL-1alpha) is a powerful activator of osteoclast cells. However, the underlying mechanism for this activation is unknown. In this study, we reveal that IL-1alpha 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-kappaB, or Genistein, a protein tyrosine kinase inhibitor, suggesting that IL-1alpha up-regulation may be via the tyrosine kinase-NF-kappaB pathway to regulate cathepsin K expression. Antisense oligonucleotides to p65, but not the p50 subunit of NF-kappaB, suppress the IL-1alpha-induced expression of cathepsin K. We therefore conclude that IL-1alpha up-regulates cathepsin K gene expression at the transcription level, and this regulation may be via the tyrosine-kinase-NF-kappaB pathway.