1. IL-1α Stimulates Cathepsin K Expression in Osteoclasts via the Tyrosine Kinase-NF-κB Pathway
- Author
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Y. Abe, S. Yang, R. Moroi, Yi-Ping Li, S. Kamolmatyakul, Wei Chen, and Amir M. Ashique
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0301 basic medicine ,Transcription, Genetic ,MAP Kinase Signaling System ,Cathepsin K ,Osteoclasts ,Cathepsin D ,Cathepsin E ,Biology ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cathepsin O ,Cathepsin H ,Osteoclast ,Cathepsin L1 ,medicine ,Animals ,Bone Resorption ,Protein Kinase Inhibitors ,General Dentistry ,Cells, Cultured ,Cathepsin ,Dose-Response Relationship, Drug ,NF-kappa B ,030206 dentistry ,Protein-Tyrosine Kinases ,Cathepsins ,Molecular biology ,Coculture Techniques ,Recombinant Proteins ,Up-Regulation ,030104 developmental biology ,medicine.anatomical_structure ,Interleukin-1 - 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.
- Published
- 2004
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