title: IL-1alpha stimulates cathepsin K expression in osteoclasts via the tyrosine kinase-NF-kappaB pathway.
abstract: 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.
authors.affiliation: Harvard-Forsyth Department of Oral Biology, The Forsyth Institute and Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kamolmatyakul
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: R
authors.initials: R
authors.lastname: Moroi
authors.forename: A M
authors.initials: AM
authors.lastname: Ashique
authors.forename: Y-P
authors.initials: YP
authors.lastname: Li
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D002403:Cathepsins; D056657:Cathepsin K; C534132:Ctsk protein, mouse