CX3CL1/fractalkine regulates the differentiation of human peripheral blood monocytes and monocyte-derived dendritic cells into osteoclasts

Cytokine. 2021 Oct:146:155652. doi: 10.1016/j.cyto.2021.155652. Epub 2021 Jul 26.

Abstract

Osteoclast differentiation is promoted under inflammatory conditions and osteoclasts play a major role in bone destruction in rheumatoid arthritis (RA). Chemokine (C-X3-C motif) ligand 1 (CX3CL1), also known as fractalkine, functions as a chemoattractant and adhesion molecule, and is involved in the pathogenesis of RA. The blockade of CX3CL1 inhibits the migration of macrophages and osteoclast precursor cells into the inflamed synovium. In the present study, we investigated the direct stimulatory effects of CX3CL1 on osteoclast differentiation from human peripheral blood monocytes and monocyte-derived dendritic cells. A stimulation with CX3CL1 significantly promoted osteoclast differentiation from CD16- monocytes and also monocyte-derived dendritic cells induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). On the other hand, CD16+ monocytes treated with M-CSF and RANKL did not differentiate into osteoclasts, even with CX3CL1. Calcium resorption was significantly increased by monocyte-derived osteoclasts, but not by dendritic cell-derived osteoclasts, following the addition of CX3CL1. The present results suggest that CX3CL1 directly regulates osteoclast differentiation. CX3CL1 may play important roles in the pathogenesis of RA, not only through the accumulation of inflammatory cells, but also through osteoclastogenesis.

Keywords: CX3CL1; CX3CR1; Dendritic cell; Fractalkine; Osteoclast; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CX3C Chemokine Receptor 1 / metabolism
  • Calcium / metabolism
  • Cell Differentiation*
  • Chemokine CX3CL1 / metabolism*
  • Dendritic Cells / cytology*
  • Humans
  • Monocytes / cytology*
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism
  • Osteogenesis
  • Receptors, IgG / metabolism

Substances

  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Chemokine CX3CL1
  • NFATC Transcription Factors
  • Receptors, IgG
  • Calcium