Inhibition of the classical NF-κB pathway prevents osteoclast bone-resorbing activity

Niroshani S. Soysa, Neil Alles, Hitoyata Shimokawa, Eijiro Jimi, Kazuhiro Aoki, Keiichi Ohya

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The classical NF-κB pathway plays an important role in osteoclast formation and differentiation; however, the role of NF-κB in osteoclast bone-resorbing activity is not well understood. To elucidate whether NF-κB is important for osteoclast bone-resorbing activity, we used a selective peptide inhibitor of the classical NF-κB pathway named the NBD peptide. Osteoclasts were generated using bone marrow macrophages in the presence of M-CSF and RANKL. The NBD peptide dose-dependently blocked the bone-resorbing activity of osteoclasts by reducing area, volume (p < 0.001) and depths (p < 0.05) of pits. The reduced resorption by the peptide was due to reduced osteoclast bone-resorbing activity, but not reduced differentiation as the number of osteoclasts was similar in all groups. The peptide inhibited bone resorption by reducing TRAP activity, disrupting actin rings and preventing osteoclast migration. Gene expressions of a panel of bone resorption markers were significantly reduced. The NBD peptide dose-dependently reduced the RANKL-induced c-Src kinase activity, which is important for actin ring formation and osteoclast bone resorption. Therefore, these data suggest that the classical NF-κB pathway plays a pivotal role in osteoclast bone-resorbing activity.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalJournal of Bone and Mineral Metabolism
Volume27
Issue number2
DOIs
Publication statusPublished - Mar 1 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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