Inhibition of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation by pyrroloquinoline quinine (PQQ)

Immunol Lett. 2012 Feb 29;142(1-2):34-40. doi: 10.1016/j.imlet.2011.12.001. Epub 2011 Dec 13.

Abstract

The effect of pyrroloquinoline quinine (PQQ) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation was examined using RAW 264.7 macrophage-like cells. RANKL led to the formation of osteoclasts identified as tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in the culture of RAW 264.7 cells. However, PQQ inhibited the appearance of osteoclasts and prevented the decrease of F4/80 macrophage maturation marker on RANKL-stimulated cells, suggesting a preventive action of PQQ on RANKL-induced osteoclast differentiation. PQQ inhibited the activation of nuclear factor of activated T cells (NFATc1), a key transcription factor of osteoclastogenesis, in RANKL-stimulated cells. On the other hand, PQQ did not inhibit the signaling pathway from RANK/RANKL binding to NFATc1 activation, including NF-κB and mitogen-activated protein kinases (MAPKs). PQQ augmented the expression of type I interferon receptor (IFNAR) and enhanced the IFN-β-mediated janus kinase (JAK1) and signal transducer and activator of transcription (STAT1) expression. Moreover, PQQ reduced the expression level of c-Fos leading to the activation of NFATc1. Taken together, PQQ was suggested to prevent RANKL-induced osteoclast formation via the inactivation of NFATc1 by reduced c-Fos expression. The reduced c-Fos expression might be mediated by the enhanced IFN-β signaling due to augmented IFNAR expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Line
  • Interferon-beta / metabolism
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • NFATC Transcription Factors / antagonists & inhibitors*
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • PQQ Cofactor / pharmacology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • RANK Ligand / metabolism
  • RANK Ligand / pharmacology*
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Receptor, Interferon alpha-beta / metabolism
  • Signal Transduction

Substances

  • Ifnar1 protein, mouse
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Proto-Oncogene Proteins c-fos
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptor, Interferon alpha-beta
  • PQQ Cofactor
  • Interferon-beta